Concomitant diagnosis of immune deficiency and Pseudomonas sepsis in a 19 month old with ecthyma gangrenosum by host whole-genome sequencing.

X-linked agammaglobulinemia (XLA, OMIM#300300) is a rare monogenic primary immunodeficiency caused by mutations in the Bruton tyrosine kinase (BTK) gene. XLA is characterized by insufficient immunoglobulin levels and susceptibility to life-threatening bacterial infections. We report on a patient that presented with ecthyma gangrenosum and septicemia. Rapid trio whole-genome sequencing (rWGS) revealed an apparently de novo hemizygous pathogenic variant (c.726dupT; p.Ile243TyrfsTer15) in the BTK gene. Metagenomic analysis of rWGS sequences that did not align to the human genome revealed 770 aligned to the Pseudomonas aeruginosa PAO1 genome. The patient was diagnosed with XLA and pseudomonal sepsis

Species Abundance Patterns in Complex Evolutionary Dynamics

An analytic theory of species abundance patterns (SAPs) in biological networks is presented. The theory is based on multispecies replicator dynamics equivalent to the Lotka-Volterra equation, with diverse interspecies interactions. Various SAPs observed in nature are derived from a single parameter. The abundance distribution is formed like a widely observed left-skewed lognormal distribution. As the model has a general form, the result can be applied to similar patterns in other complex biological networks, e.g. gene expression.Comment: 4 pages, 3 figures. Physical Review Letters, in pres

Statistical mechanics and stability of a model eco-system

We study a model ecosystem by means of dynamical techniques from disordered systems theory. The model describes a set of species subject to competitive interactions through a background of resources, which they feed upon. Additionally direct competitive or co-operative interaction between species may occur through a random coupling matrix. We compute the order parameters of the system in a fixed point regime, and identify the onset of instability and compute the phase diagram. We focus on the effects of variability of resources, direct interaction between species, co-operation pressure and dilution on the stability and the diversity of the ecosystem. It is shown that resources can be exploited optimally only in absence of co-operation pressure or direct interaction between species.Comment: 23 pages, 13 figures; text of paper modified, discussion extended, references adde

Non-isothermal model for the direct isotropic/smectic-A liquid crystalline transition

An extension to a high-order model for the direct isotropic/smectic-A liquid crystalline phase transition was derived to take into account thermal effects including anisotropic thermal diffusion and latent heat of phase-ordering. Multi-scale multi-transport simulations of the non-isothermal model were compared to isothermal simulation, showing that the presented model extension corrects the standard Landau-de Gennes prediction from constant growth to diffusion-limited growth, under shallow quench/undercooling conditions. Non-isothermal simulations, where meta-stable nematic pre-ordering precedes smectic-A growth, were also conducted and novel non-monotonic phase-transformation kinetics observed.Comment: First revision: 20 pages, 7 figure

Rank abundance relations in evolutionary dynamics of random replicators

We present a non-equilibrium statistical mechanics description of rank abundance relations (RAR) in random community models of ecology. Specifically, we study a multi-species replicator system with quenched random interaction matrices. We here consider symmetric interactions as well as asymmetric and anti-symmetric cases. RARs are obtained analytically via a generating functional analysis, describing fixed-point states of the system in terms of a small set of order parameters, and in dependence on the symmetry or otherwise of interactions and on the productivity of the community. Our work is an extension of Tokita [Phys. Rev. Lett. {\bf 93} 178102 (2004)], where the case of symmetric interactions was considered within an equilibrium setup. The species abundance distribution in our model come out as truncated normal distributions or transformations thereof and, in some case, are similar to left-skewed distributions observed in ecology. We also discuss the interaction structure of the resulting food-web of stable species at stationarity, cases of heterogeneous co-operation pressures as well as effects of finite system size and of higher-order interactions.Comment: 12 pages, 14 figures; text amended, minor corrections/modifications to figure

Spring School on Language, Music, and Cognition: Organizing Events in Time

The interdisciplinary spring school “Language, music, and cognition: Organizing events in time” was held from February 26 to March 2, 2018 at the Institute of Musicology of the University of Cologne. Language, speech, and music as events in time were explored from different perspectives including evolutionary biology, social cognition, developmental psychology, cognitive neuroscience of speech, language, and communication, as well as computational and biological approaches to language and music. There were 10 lectures, 4 workshops, and 1 student poster session. Overall, the spring school investigated language and music as neurocognitive systems and focused on a mechanistic approach exploring the neural substrates underlying musical, linguistic, social, and emotional processes and behaviors. In particular, researchers approached questions concerning cognitive processes, computational procedures, and neural mechanisms underlying the temporal organization of language and music, mainly from two perspectives: one was concerned with syntax or structural representations of language and music as neurocognitive systems (i.e., an intrapersonal perspective), while the other emphasized social interaction and emotions in their communicative function (i.e., an interpersonal perspective). The spring school not only acted as a platform for knowledge transfer and exchange but also generated a number of important research questions as challenges for future investigations

Understanding signaling cascades in melanoma

Understanding regulatory pathways involved in melanoma development and progression has advanced significantly in recent years. It is now appreciated that melanoma is the result of complex changes in multiple signaling pathways that affect growth control, metabolism, motility and the ability to escape cell death programs. Here we review the major signaling pathways currently known to be deregulated in melanoma with an implication to its development and progression. Among these pathways are Ras, B-Raf, MEK, PTEN, phosphatidylinositol-3 kinase (PI3Ks) and Akt which are constitutively activated in a significant number of melanoma tumors, in most cases due to genomic change. Other pathways discussed in this review include the [Janus kinase/signal transducer and activator of transcription (JAK/STAT), transforming growth factor-beta pathways which are also activated in melanoma, although the underlying mechanism is not yet clear. As a paradigm for remodeled signaling pathways, melanoma also offers a unique opportunity for targeted drug development.Fil: Lopez Bergami, Pablo Roberto. Sanford-burnham Medical Research Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Fitchmann, B. Sanford-burnham Medical Research Institute; Estados UnidosFil: Ronai, Ze´ev. Sanford-burnham Medical Research Institute; Estados Unido

Association of angiopoietin-like protein 3 with hepatic triglyceride lipase and lipoprotein lipase activities in human plasma

金沢大学医学系研究科Background: The relationship between plasma angiopoietin-like protein 3 (ANGPTL3), and lipoprotein lipase (LPL) activity and hepatic triglyceride lipase (HTGL) activity has not been investigated in the metabolism of remnant lipoproteins (RLPs) and high-density lipoprotein (HDL) in human plasma. Methods: ANGPTL3, LPL activity, HTGL activity, RLP-C and RLP-TG and small, dense LDL-cholesterol (sd LDL-C) were measured in 20 overweight and obese subjects in the fasting and postprandial states. Results: Plasma TG, RLP-C, RLP-TG and sd LDL-C were inversely correlated with LPL activity both in the fasting and postprandial states, but not correlated with HTGL activity and ANGPTL3. However, plasma HDL-C was positively correlated with LPL activity both in the fasting and postprandial states, while inversely correlated with HTGL activity. ANGPTL3 was inversely correlated with HTGL activity both in the fasting and postprandial states, but not correlated with LPL activity. Conclusion: HTGL plays a major role in HDL metabolism, but not RLP metabolism. These findings suggest that ANGPTL3 is strongly associated with the inhibition of HTGL activity and regulates HDL metabolism, but not associated with the inhibition of LPL activity for the metabolism of RLPs in human plasma

The Hubble Space Telescope Cluster Supernova Survey: V. Improving the Dark Energy Constraints Above z>1 and Building an Early-Type-Hosted Supernova Sample

We present ACS, NICMOS, and Keck AO-assisted photometry of 20 Type Ia supernovae SNe Ia from the HST Cluster Supernova Survey. The SNe Ia were discovered over the redshift interval 0.623 < z < 1.415. Fourteen of these SNe Ia pass our strict selection cuts and are used in combination with the world's sample of SNe Ia to derive the best current constraints on dark energy. Ten of our new SNe Ia are beyond redshift $z=1$, thereby nearly doubling the statistical weight of HST-discovered SNe Ia beyond this redshift. Our detailed analysis corrects for the recently identified correlation between SN Ia luminosity and host galaxy mass and corrects the NICMOS zeropoint at the count rates appropriate for very distant SNe Ia. Adding these supernovae improves the best combined constraint on the dark energy density \rho_{DE}(z) at redshifts 1.0 < z < 1.6 by 18% (including systematic errors). For a LambdaCDM universe, we find \Omega_\Lambda = 0.724 +0.015/-0.016 (68% CL including systematic errors). For a flat wCDM model, we measure a constant dark energy equation-of-state parameter w = -0.985 +0.071/-0.077 (68% CL). Curvature is constrained to ~0.7% in the owCDM model and to ~2% in a model in which dark energy is allowed to vary with parameters w_0 and w_a. Tightening further the constraints on the time evolution of dark energy will require several improvements, including high-quality multi-passband photometry of a sample of several dozen z>1 SNe Ia. We describe how such a sample could be efficiently obtained by targeting cluster fields with WFC3 on HST.Comment: 27 pages, 11 figures. Submitted to ApJ. This first posting includes updates in response to comments from the referee. See http://www.supernova.lbl.gov for other papers in the series pertaining to the HST Cluster SN Survey. The updated supernova Union2.1 compilation of 580 SNe is available at http://supernova.lbl.gov/Unio