Patterns of subnet usage reveal distinct scales of regulation in the transcriptional regulatory network of Escherichia coli

The set of regulatory interactions between genes, mediated by transcription factors, forms a species' transcriptional regulatory network (TRN). By comparing this network with measured gene expression data one can identify functional properties of the TRN and gain general insight into transcriptional control. We define the subnet of a node as the subgraph consisting of all nodes topologically downstream of the node, including itself. Using a large set of microarray expression data of the bacterium Escherichia coli, we find that the gene expression in different subnets exhibits a structured pattern in response to environmental changes and genotypic mutation. Subnets with less changes in their expression pattern have a higher fraction of feed-forward loop motifs and a lower fraction of small RNA targets within them. Our study implies that the TRN consists of several scales of regulatory organization: 1) subnets with more varying gene expression controlled by both transcription factors and post-transcriptional RNA regulation, and 2) subnets with less varying gene expression having more feed-forward loops and less post-transcriptional RNA regulation.Comment: 14 pages, 8 figures, to be published in PLoS Computational Biolog

Radiation therapy generates platelet-activating factor agonists

Pro-oxidative stressors can suppress host immunity due to their ability to generate oxidized lipid agonists of the platelet-activating factor-receptor (PAF-R). As radiation therapy also induces reactive oxygen species, the present studies were designed to define whether ionizing radiation could generate PAF-R agonists and if these lipids could subvert host immunity. We demonstrate that radiation exposure of multiple tumor cell lines in-vitro, tumors in-vivo, and human subjects undergoing radiation therapy for skin tumors all generate PAF-R agonists. Structural characterization of radiation-induced PAF-R agonistic activity revealed PAF and multiple oxidized glycerophosphocholines that are produced non-enzymatically. In a murine melanoma tumor model, irradiation of one tumor augmented the growth of the other (non-treated) tumor in a PAF-R-dependent process blocked by a cyclooxygenase-2 inhibitor. These results indicate a novel pathway by which PAF-R agonists produced as a byproduct of radiation therapy could result in tumor treatment failure, and offer important insights into potential therapeutic strategies that could improve the overall antitumor effectiveness of radiation therapy regimens

Mortalidad de aves marinas producida por luces artificiales terrestres

Artificial lights at night cause high mortality of seabirds, one of the most endangered groups of birds globally. Fledglings of burrow-nesting seabirds, and to a lesser extent adults, are attracted to and then grounded (i.e., forced to land) by lights when they fly at night. We reviewed the current state of knowledge of seabird attraction to light to identify information gaps and propose measures to address the problem. Although species in families such as Alcidae and Anatidae can be grounded by artificial light, the most affected seabirds are petrels and shearwaters (Procellariiformes). At least 56 species of Procellariiformes, more than one-third of them (24) threatened, are subject to grounding by lights. Seabirds grounded by lights have been found worldwide, mainly on oceanic islands but also at some continental locations. Petrel breeding grounds confined to formerly uninhabited islands are particularly at risk from light pollution due to tourism and urban sprawl. Where it is impractical to ban external lights, rescue programs of grounded birds offer the most immediate and employed mitigation to reduce the rate of light-induced mortality and save thousands of birds every year. These programs also provide useful information for seabird management. However, these data are typically fragmentary, biased, and uncertain and can lead to inaccurate impact estimates and poor understanding of the phenomenon of seabird attraction to lights. We believe the most urgently needed actions to mitigate and understand light-induced mortality of seabirds are estimation of mortality and effects on populations; determination of threshold light levels and safe distances from light sources; documentation of the fate of rescued birds; improvement of rescue campaigns, particularly in terms of increasing recovery rates and level of care; and research on seabird-friendly lights to reduce attraction.RESUMEN: Las luces artificiales nocturnas causan una mortalidad alta de aves marinas, uno de los grupos de aves en mayor peligro de extinción a nivel mundial. Los polluelos de aves marinas que anidan en madrigueras, y en menor medida los adultos, son atraídos y forzados a aterrizar por las luces cuando vuelan de noche. Revisamos el estado actual del conocimiento sobre la atracción de las aves marinas por la luz para identificar vacíos de información y proponer medidas para resolver el problema. Aunque las especies de familias como Alcidae y Anatidae pueden ser forzadas a aterrizar por la luz artificial, las aves marinas más afectadas son los petreles y las pardelas (Procellariiformes). Por lo menos 56 especies de Procellariiformes, más de un tercio (24) de ellas amenazadas, son propensas al aterrizaje atraídas por las luces. Las aves marinas forzadas a aterrizar han sido halladas en todo el mundo, principalmente en islas oceánicas, pero también en algunas localidades continentales. Los sitios de anidación de los petreles confinados anteriormente a islas deshabitadas están particularmente en riesgo de sufrir contaminación lumínica debido al turismo y al crecimiento urbano. En donde no es práctico prohibir las luces externas, los programas de rescate de las aves accidentadas ofrecen la mitigación más inmediata y empleada para reducir la tasa de mortalidad inducida por la luz y salvar a miles de aves cada año. Estos programas también proporcionan información útil para el manejo de aves marinas. Sin embargo, estos datos están típicamente fragmentados, sesgados y son inciertos, y pueden llevar a estimaciones inexactas del impacto y a un entendimiento pobre del fenómeno de la atracción de las aves marinas por la luz. Creemos que las acciones necesarias de mayor urgencia para mitigar y entender la mortalidad de aves marinas producida por la luz son: la estimación de la mortalidad y los efectos sobre la población; la determinación de umbrales de niveles de luz y de distancias seguras a las fuentes de luz; el estudio del destino de las aves rescatadas; la mejora de las campañas de rescate, particularmente en términos de incrementar las tasas de recogida y el nivel de cuidado; y la investigación sobre las características de la luz para reducir la atracción de las aves marinas.This research was supported by a Marie Curie Intra European Fellowship within the 7th European Community Framework Programme (Project ID: 330655 FP7-PEOPLE-2012-IOF)info:eu-repo/semantics/publishedVersio

An All-Atom Model of the Chromatin Fiber Containing Linker Histones Reveals a Versatile Structure Tuned by the Nucleosomal Repeat Length

In the nucleus of eukaryotic cells, histone proteins organize the linear genome into a functional and hierarchical architecture. In this paper, we use the crystal structures of the nucleosome core particle, B-DNA and the globular domain of H5 linker histone to build the first all-atom model of compact chromatin fibers. In this 3D jigsaw puzzle, DNA bending is achieved by solving an inverse kinematics problem. Our model is based on recent electron microscopy measurements of reconstituted fiber dimensions. Strikingly, we find that the chromatin fiber containing linker histones is a polymorphic structure. We show that different fiber conformations are obtained by tuning the linker histone orientation at the nucleosomes entry/exit according to the nucleosomal repeat length. We propose that the observed in vivo quantization of nucleosomal repeat length could reflect nature's ability to use the DNA molecule's helical geometry in order to give chromatin versatile topological and mechanical properties

Lsr2 of Mycobacterium tuberculosis is a DNA-bridging protein

Lsr2 is a small, basic protein present in Mycobacterium and related actinomycetes. Recent studies suggest that Lsr2 is a regulatory protein involved in multiple cellular processes including cell wall biosynthesis and antibiotic resistance. However, the underlying molecular mechanisms remain unknown. In this article, we performed biochemical studies of Lsr2–DNA interactions and structure–function analysis of Lsr2. Analysis by atomic force microscopy revealed that Lsr2 has the ability to bridge distant DNA segments, suggesting that Lsr2 plays a role in the overall organization and compactness of the nucleoid. Mutational analysis identified critical residues and selection of dominant negative mutants demonstrated that both DNA binding and protein oligomerization are essential for the normal functions of Lsr2 in vivo. These results provide strong evidence that Lsr2 is a DNA bridging protein, which represents the first identification of such proteins in bacteria phylogenetically distant from the Enterobacteriaceae. DNA bridging by Lsr2 also provides a mechanism of transcriptional regulation by Lsr2

Joint ICES-SEAwise workshop to quality assure methods to incorporate environmental factors and quantifying ecological considerations in management strategy evaluation tools (WKEcoMSE)

The EU project SEAwise (https://seawiseproject.org/) endeavours to enhance existing multi-stock multi-species Management Strategy Evaluation (MSE) models so that they can be used to define and evaluate fisheries management strategies that address broad Ecosystem-Based Fisheries Management (EBFM) objectives, including in particular identifying Harvest Control Rules (HCRs) that are robust to changes in productivity. The WKEcoMSE workshop was held to: (1) benchmark the approaches used or developed in the project to develop robust and consistent environment-productivity relationships for commercial stocks across selected case studies and integrate them in MSE models used by the SEAwise project and by ICES; (2) to provide context for those approaches within the general field of “environment-enriched” MSEs; and (3) to draw from the participants collective experience some general guidelines about the integration of environmental impacts on stock productivity in MSE tools. 23 presentations were given, both about the work carried out within SEAwise but also by international colleagues working toward similar objectives, and various topics were discussed over eight sessions designed to accommodate participants spread across Europe and Northern America. “Good practices” to incorporate environmental considerations in MSE modelling were then drafted collectively and have been summarized in the panels below. These rely on the experiences of the WKEcoMSE participants and are not exhaustive.info:eu-repo/semantics/publishedVersio

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI