A quantitative comparison of sRNA-based and protein-based gene regulation

Small, non-coding RNAs (sRNAs) play important roles as genetic regulators in prokaryotes. sRNAs act post-transcriptionally via complementary pairing with target mRNAs to regulate protein expression. We use a quantitative approach to compare and contrast sRNAs with conventional transcription factors (TFs) to better understand the advantages of each form of regulation. In particular, we calculate the steady-state behavior, noise properties, frequency-dependent gain (amplification), and dynamical response to large input signals of both forms of regulation. While the mean steady-state behavior of sRNA-regulated proteins exhibits a distinctive tunable threshold-linear behavior, our analysis shows that transcriptional bursting leads to significantly higher intrinsic noise in sRNA-based regulation than in TF-based regulation in a large range of expression levels and limits the ability of sRNAs to perform quantitative signaling. Nonetheless, we find that sRNAs are better than TFs at filtering noise in input signals. Additionally, we find that sRNAs allow cells to respond rapidly to large changes in input signals. These features suggest a niche for sRNAs in allowing cells to transition quickly yet reliably between distinct states. This functional niche is consistent with the widespread appearance of sRNAs in stress-response and quasi-developmental networks in prokaryotes.Comment: 26 pages, 8 figures; accepted for publication in Molecular Systems Biolog

Cerebrofaciothoracic dysplasia: four new patients with a recurrent TMCO1 pathogenic variant.

Biallelic loss of function variants in the TMCO1 gene have been previously demonstrated to result in cerebrofaciothoracic dysplasia (CFTD; MIM #213980). The phenotype of this condition includes severe intellectual disability, as well as distinctive craniofacial features, including brachycephaly, synophrys, arched eyebrows, "cupid's bow" upper lip, and microdontia. In addition, nonspecific skeletal anomalies are common, including bifid ribs, scoliosis, and spinal fusion. Only 19 molecularly confirmed patients have been previously described. Here, we present four patients with CFTD, including three brothers from a Pakistani background and an additional unrelated white Scottish patient. All share the characteristic craniofacial appearance, with severe intellectual disability and skeletal abnormalities. We further define the phenotype with comparison to the published literature, and present images to define the dysmorphic features in a previously unreported ethnic group. All of our patient series are homozygous for the same c.292_293del (p.Ser98*) TMCO1 pathogenic variant, which has been previously reported only in an isolated Amish population. Thus we provide evidence that CFTD may be more common than previously thought. The patients presented here further delineate the phenotypic spectrum of CFTD and provide evidence for a recurrent pathogenic variant in TMCO1

The X-ray luminosity of solar-mass stars in the intermediate age open cluster NGC 752

AIMS. While observational evidence shows that most of the decline in a star's X-ray activity occurs between the age of the Hyades (~8 x 10^8 yrs) and that of the Sun, very little is known about the evolution of stellar activity between these ages. To gain information on the typical level of coronal activity at a star's intermediate age, we studied the X-ray emission from stars in the 1.9 Gyr old open cluster NGC 752. METHODS. We analysed a ~140 ks Chandra observation of NGC 752 and a ~50 ks XMM-Newton observation of the same cluster. We detected 262 X-ray sources in the Chandra data and 145 sources in the XMM-Newton observation. Around 90% of the catalogued cluster members within Chandra's field-of-view are detected in the X-ray. The X-ray luminosity of all observed cluster members (28 stars) and of 11 cluster member candidates was derived. RESULTS. Our data indicate that, at an age of 1.9 Gyr, the typical X-ray luminosity of the cluster members with M=0.8-1.2 Msun is Lx = 1.3 x 10^28 erg s^-1, so approximately a factor of 6 less intense than that observed in the younger Hyades. Given that Lx is proportional to the square of a star's rotational rate, the median Lx of NGC 752 is consistent, for t > 1 Gyr, to a decaying rate in rotational velocities v_rot ~ t^-alpha with alpha ~ 0.75, steeper than the Skumanich relation (alpha ~ 0.5) and significantly steeper than observed between the Pleiades and the Hyades (where alpha < 0.3), suggesting that a change in the rotational regimes of the stellar interiors is taking place at t ~ 1 Gyr.Comment: Accepted for publication in A&A (13 pages, 8 figures

Guaranteed clustering and biclustering via semidefinite programming

Identifying clusters of similar objects in data plays a significant role in a wide range of applications. As a model problem for clustering, we consider the densest k-disjoint-clique problem, whose goal is to identify the collection of k disjoint cliques of a given weighted complete graph maximizing the sum of the densities of the complete subgraphs induced by these cliques. In this paper, we establish conditions ensuring exact recovery of the densest k cliques of a given graph from the optimal solution of a particular semidefinite program. In particular, the semidefinite relaxation is exact for input graphs corresponding to data consisting of k large, distinct clusters and a smaller number of outliers. This approach also yields a semidefinite relaxation for the biclustering problem with similar recovery guarantees. Given a set of objects and a set of features exhibited by these objects, biclustering seeks to simultaneously group the objects and features according to their expression levels. This problem may be posed as partitioning the nodes of a weighted bipartite complete graph such that the sum of the densities of the resulting bipartite complete subgraphs is maximized. As in our analysis of the densest k-disjoint-clique problem, we show that the correct partition of the objects and features can be recovered from the optimal solution of a semidefinite program in the case that the given data consists of several disjoint sets of objects exhibiting similar features. Empirical evidence from numerical experiments supporting these theoretical guarantees is also provided

Dimensionality and dynamics in the behavior of C. elegans

A major challenge in analyzing animal behavior is to discover some underlying simplicity in complex motor actions. Here we show that the space of shapes adopted by the nematode C. elegans is surprisingly low dimensional, with just four dimensions accounting for 95% of the shape variance, and we partially reconstruct "equations of motion" for the dynamics in this space. These dynamics have multiple attractors, and we find that the worm visits these in a rapid and almost completely deterministic response to weak thermal stimuli. Stimulus-dependent correlations among the different modes suggest that one can generate more reliable behaviors by synchronizing stimuli to the state of the worm in shape space. We confirm this prediction, effectively "steering" the worm in real time.Comment: 9 pages, 6 figures, minor correction

Adiponectin Reduces Plasma Triglyceride by Increasing VLDL Triglyceride Catabolism

OBJECTIVE—Adiponectin is an adipocyte-derived hormone that plays an important role in glucose and lipid metabolism. The main aims of this study are to investigate the effects of adiponectin on VLDL triglyceride (VLDL-TG) metabolism and the underlying mechanism

SCN8A encephalopathy: Research progress and prospects

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133635/1/epi13422.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133635/2/epi13422_am.pd

Genetic and Transmission Analysis of Helicobacter pylori Strains within a Family1

Point mutations, intragenic recombination, and introduction of foreign alleles enhanced strain diversity within the family

Gas-phase and particulate products from the atmospheric degradation of an isoxazole fungicide

[EN] The isoxazole structure is present in several pesticides. However, there is a lack of information about its degradation products after the release to the atmosphere. The main atmospheric reactions of hymexazol (5-methylisoxazol-3-ol), selected as representative model, were investigated at a large outdoor simulation chamber. The predominant products of atmospheric degradations were gaseous nitrogen derivates (nitric acid, nitrogen dioxide, nitrogen oxide, nitrous acid, and peroxyacetylnitrate), ozone, and small oxygenated compounds (formic acid, formaldehyde, and methylglyoxal). The aerosol yields were lower than 5%, and an OH rate-dependence was observed in the nucleation, particle growth, and size distribution. Also, the chemical composition of minor multi-oxygenated products was studied for OH-photooxidations. More than 20 products were detected in the gas or particulate phase. The most abundant were heterocyclic cleavage products with C4-chain and oxygenated moieties at positions 1 and 3, such as 3,4-dioxobutanoic acid, 3-oxobutanoic acid, and 3-oxobutanal. The suggested reaction pathway is the opening of heterocycle ring by the cleavage of N O bond and C N bond, releasing nitrogen oxides.The authors wish to thank the EUPHORE staff and J.T.B. The authors wish to acknowledge Ministerio de Ciencia y Tecnologia for IMPESTAT (CGL2010-18474/CLI) and the European Community's Seventh Framework Program under the Grant agreement no. 228335 (Eurochamp2). The Fundacion CEAM is partly supported by Generalitat Valenciana, and the projects GRACCIE (Consolider-Ingenio 2010) and FEEDBACKS (Prometeo - Generalitat Valenciana). EUPHORE instrumentation is partly funded by the Spanish Ministry of Science and Innovation, through INNPLANTA Project: PCT-440000-2010-003.Tortajada-Genaro, LA.; Borrás García, EM.; Muñoz, A. (2013). Gas-phase and particulate products from the atmospheric degradation of an isoxazole fungicide. Chemosphere. 92(8):1035-1041. https://doi.org/10.1016/j.chemosphere.2013.03.041S1035104192

Driving chronicity in rheumatoid arthritis: perpetuating role of myeloid cells

Acute inflammation is a complex and tightly regulated homeostatic process that includes leukocyte migration from the vasculature into tissues to eliminate the pathogen/injury, followed by a pro-resolving response promoting tissue repair. However, if inflammation is uncontrolled as in chronic diseases such as Rheumatoid Arthritis (RA) it leads to tissue damage and disability. Synovial tissue inflammation in RA patients is maintained by sustained activation of multiple inflammatory positive-feedback regulatory pathways in a variety of cells including myeloid cells. In this review, we will highlight recent evidence uncovering biological mechanisms contributing to the aberrant activation of myeloid cells that contributes to perpetuation of inflammation in RA, and discuss emerging data on anti-inflammatory mediators contributing to sustained remission that may inform a novel category of therapeutic targets