Quantitative chemometric phenotyping of three-dimensional liver organoids by Raman spectral imaging

Confocal Raman spectral imaging (RSI) enables high-content, label-free visualization of a wide range of molecules in biological specimens without sample preparation. However, reliable quantification of the deconvoluted spectra is needed. Here we develop an integrated bioanalytical methodology, qRamanomics, to qualify RSI as a tissue phantom calibrated tool for quantitative spatial chemotyping of major classes of biomolecules. Next, we apply qRamanomics to fixed 3D liver organoids generated from stem-cell-derived or primary hepatocytes to assess specimen variation and maturity. We then demonstrate the utility of qRamanomics for identifying biomolecular response signatures from a panel of liver-altering drugs, probing drug-induced compositional changes in 3D organoids followed by in situ monitoring of drug metabolism and accumulation. Quantitative chemometric phenotyping constitutes an important step in developing quantitative label-free interrogation of 3D biological specimens

The Imperfect Fluid behind Kinetic Gravity Braiding

We present a standard hydrodynamical description for non-canonical scalar field theories with kinetic gravity braiding. In particular, this picture applies to the simplest galileons and k-essence. The fluid variables not only have a clear physical meaning but also drastically simplify the analysis of the system. The fluid carries charges corresponding to shifts in field space. This shift-charge current contains a spatial part responsible for diffusion of the charges. Moreover, in the incompressible limit, the equation of motion becomes the standard diffusion equation. The fluid is indeed imperfect because the energy flows neither along the field gradient nor along the shift current. The fluid has zero vorticity and is not dissipative: there is no entropy production, the energy-momentum is exactly conserved, the temperature vanishes and there is no shear viscosity. Still, in an expansion around a perfect fluid one can identify terms which correct the pressure in the manner of bulk viscosity. We close by formulating the non-trivial conditions for the thermodynamic equilibrium of this imperfect fluid.Comment: 23 pages plus appendices. New version includes extended discussion on diffusion and dynamics in alternative frames, as well as additional references. v3 reflects version accepted for publication in JHEP: minor comments added regarding suitability to numerical approache

Regionalização para o cultivo do feijão no Rio Grande do Sul com base na interação genótipo x ambiente¹.

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Scans for signatures of selection in Russian cattle breed genomes reveal new candidate genes for environmental adaptation and acclimation

Domestication and selective breeding has resulted in over 1000 extant cattle breeds. Many of these breeds do not excel in important traits but are adapted to local environments. These adaptations are a valuable source of genetic material for efforts to improve commercial breeds. As a step toward this goal we identified candidate regions to be under selection in genomes of nine Russian native cattle breeds adapted to survive in harsh climates. After comparing our data to other breeds of European and Asian origins we found known and novel candidate genes that could potentially be related to domestication, economically important traits and environmental adaptations in cattle. The Russian cattle breed genomes contained regions under putative selection with genes that may be related to adaptations to harsh environments (e.g., AQP5, RAD50, and RETREG1). We found genomic signatures of selective sweeps near key genes related to economically important traits, such as the milk production (e.g., DGAT1, ABCG2), growth (e.g., XKR4), and reproduction (e.g., CSF2). Our data point to candidate genes which should be included in future studies attempting to identify genes to improve the extant breeds and facilitate generation of commercial breeds that fit better into the environments of Russia and other countries with similar climates

Speech Graphs Provide a Quantitative Measure of Thought Disorder in Psychosis

Background: Psychosis has various causes, including mania and schizophrenia. Since the differential diagnosis of psychosis is exclusively based on subjective assessments of oral interviews with patients, an objective quantification of the speech disturbances that characterize mania and schizophrenia is in order. In principle, such quantification could be achieved by the analysis of speech graphs. A graph represents a network with nodes connected by edges; in speech graphs, nodes correspond to words and edges correspond to semantic and grammatical relationships. Methodology/Principal Findings: To quantify speech differences related to psychosis, interviews with schizophrenics, manics and normal subjects were recorded and represented as graphs. Manics scored significantly higher than schizophrenics in ten graph measures. Psychopathological symptoms such as logorrhea, poor speech, and flight of thoughts were grasped by the analysis even when verbosity differences were discounted. Binary classifiers based on speech graph measures sorted schizophrenics from manics with up to 93.8% of sensitivity and 93.7% of specificity. In contrast, sorting based on the scores of two standard psychiatric scales (BPRS and PANSS) reached only 62.5% of sensitivity and specificity. Conclusions/Significance: The results demonstrate that alterations of the thought process manifested in the speech of psychotic patients can be objectively measured using graph-theoretical tools, developed to capture specific features of the normal and dysfunctional flow of thought, such as divergence and recurrence. The quantitative analysis of speech graphs is not redundant with standard psychometric scales but rather complementary, as it yields a very accurate sorting of schizophrenics and manics. Overall, the results point to automated psychiatric diagnosis based not on what is said, but on how it is said.FINEP [01.06.1092.00]FINEPCNPq Universal [481506/2007-1]CNPq UniversalCNPqCNPqCapesCAPESad Associacao Alberto Santos Dumont para Apoio a Pesquisa (AASDAP)a'd Associacao Alberto Santos Dumont para Apoio a Pesquisa (AASDAP

Low appendicular muscle mass is correlated with femoral neck bone mineral density loss in postmenopausal women

<p>Abstract</p> <p>Background</p> <p>After menopause, rapid bone mass loss occurs in response to hypoestrogenism. Several studies suggest that muscle mass and bone mineral density (BMD) are positively associated in postmenopausal women. Therefore, it may be assumed that postmenopausal low appendicular muscle mass (aMM) can increase BMD loss in a short period of time.</p> <p>Objective</p> <p>The purpose of this study was to assess relationship of aMM with femoral neck BMD in postmenopausal women.</p> <p>Methods</p> <p>Prospective, controlled clinical Trial including 64 women aged 45-70 years, who had not had their last menstruation for at least one year. Subjects were divided into two groups: low aMM (n = 32), and normal aMM (n-32). Femoral neck BMD and muscle mass were measured by DXA at baseline and after twelve months. Pairwise and independent t tests were used for data analysis.</p> <p>Results</p> <p>Baseline weight, BMI and muscle mass (total and appendicular) significantly differ between groups (p < 0.05). After twelve months, femoral neck BMD was significantly lower in the group with low aMM, whereas no significant difference was observed in the group with normal aMM (p < 0.05).</p> <p>Conclusion</p> <p>In postmenopausal women, low appendicular muscle mass is associated negatively with femoral neck BMD in a short period of time.</p

A Single Nucleotide in Stem Loop II of 5′-Untranslated Region Contributes to Virulence of Enterovirus 71 in Mice

BACKGROUND: Enterovirus 71 (EV71) has emerged as a neuroinvasive virus responsible for several large outbreaks in the Asia-Pacific region while virulence determinant remains unexplored. PRINCIPAL FINDINGS: In this report, we investigated increased virulence of unadapted EV71 clinical isolate 237 as compared with isolate 4643 in mice. A fragment 12 nucleotides in length in stem loop (SL) II of 237 5'-untranslated region (UTR) visibly reduced survival time and rate in mice was identified by constructing a series of infectious clones harboring chimeric 5'-UTR. In cells transfected with bicistronic plasmids, and replicon RNAs, the 12-nt fragment of isolate 237 enhanced translational activities and accelerated replication of subgenomic EV71. Finally, single nucleotide change from cytosine to uridine at base 158 in this short fragment of 5'-UTR was proven to reduce viral translation and EV71 virulence in mice. Results collectively indicated a pivotal role of novel virulence determinant C158 on virus translation in vitro and EV71 virulence in vivo. CONCLUSIONS: These results presented the first reported virulence determinant in EV71 5'-UTR and first position discovered from unadapted isolates

T Helper 1–Inducing Adjuvant Protects against Experimental Paracoccidioidomycosis

Immunostimulatory therapy is a promising approach to improving the treatment of systemic fungal infections such as paracoccidioidomycosis (PCM), whose drug therapy is usually prolonged and associated with toxic side effects and relapses. The current study was undertaken to determine if the injection of a T helper (Th) 1–stimulating adjuvant in P. brasiliensis–infected mice could have a beneficial effect on the course of experimental PCM. For this purpose, mice were infected and treated with complete Freund's adjuvant (CFA), a well-established Th1 experimental inductor, or incomplete Freund's adjuvant (IFA - control group) on day 20 postinfection. Four weeks after treatment, the CFA-treated mice presented a mild infection in the lungs characterized by absence of epithelioid cell granulomas and yeast cells, whereas the control mice presented multiple sites of focal epithelioid granulomas with lymphomonocytic halos circumscribing a high number of viable and nonviable yeast cells. In addition, CFA administration induced a 2.4 log reduction (>99%) in the fungal burden when compared to the control group, and led to an improvement of immune response, reversing the immunosuppression observed in the control group. The immunotherapy with Th1-inducing adjuvant, approved to be used in humans, might be a valuable tool in the treatment of PCM and potentially useful to improve the clinical cure rate in humans