Relating the metatranscriptome and metagenome of the human gut

Although the composition of the human microbiome is now wellstudied, the microbiota’s \u3e8 million genes and their regulation remain largely uncharacterized. This knowledge gap is in part because of the difficulty of acquiring large numbers of samples amenable to functional studies of the microbiota. We conducted what is, to our knowledge, one of the first human microbiome studies in a well-phenotyped prospective cohort incorporating taxonomic, metagenomic, and metatranscriptomic profiling at multiple body sites using self-collected samples. Stool and saliva were provided by eight healthy subjects, with the former preserved by three different methods (freezing, ethanol, and RNAlater) to validate self-collection. Within-subject microbial species, gene, and transcript abundances were highly concordant across sampling methods, with only a small fraction of transcripts (\u3c5%) displaying between-method variation. Next, we investigated relationships between the oral and gut microbial communities, identifying a subset of abundant oral microbes that routinely survive transit to the gut, but with minimal transcriptional activity there. Finally, systematic comparison of the gut metagenome and metatranscriptome revealed that a substantial fraction (41%) of microbial transcripts were not differentially regulated relative to their genomic abundances. Of the remainder, consistently underexpressed pathways included sporulation and amino acid biosynthesis, whereas up-regulated pathways included ribosome biogenesis and methanogenesis. Across subjects, metatranscriptional profiles were significantly more individualized than DNA-level functional profiles, but less variable than microbial composition, indicative of subject-specific whole-community regulation. The results thus detail relationships between community genomic potential and gene expression in the gut, and establish the feasibility of metatranscriptomic investigations in subject-collected and shipped samples

A Disproportionate Response? The 2015 Proportionality Amendments to Federal Rule of Civil Procedure 26(b)

On December 1, 2015, a set of amendments to the Federal Rules of Civil Procedure took effect. Among the most significant and contentious of these changes is the Rules’ renewed focus on the concept of proportionality in the scope of discovery, added in an effort to curb perceived over-discovery. This Note argues that the new Rule 26(b) is not likely to substantially further the Committee’s professed goals. Specifically, this Note shows that, even if over-discovery is a rampant problem with proportionality as its solution—a contention that is not well supported by empirical evidence—the new Rule 26(b) does little that will effect change in federal civil litigation practice

Gelation as arrested phase separation in short-ranged attractive colloid-polymer mixtures

We present further evidence that gelation is an arrested phase separation in attractive colloid-polymer mixtures, based on a method combining confocal microscopy experiments with numerical simulations recently established in {\bf Nature 453, 499 (2008)}. Our results are independent of the form of the interparticle attractive potential, and therefore should apply broadly to any attractive particle system with short-ranged, isotropic attractions. We also give additional characterization of the gel states in terms of their structure, inhomogeneous character and local density.Comment: 6 figures, to be published in J. Phys. Condens. Matter, special issue for EPS Liquids Conference 200

Simultaneous generation of many RNA-seq libraries in a single reaction

Although RNA-seq is a powerful tool, the considerable time and cost associated with library construction has limited its utilization for various applications. RNAtag-Seq, an approach to generate multiple RNA-seq libraries in a single reaction, lowers time and cost per sample, and it produces data on prokaryotic and eukaryotic samples that are comparable to those generated by traditional strand-specific RNA-seq approaches

Timescales of Massive Human Entrainment

The past two decades have seen an upsurge of interest in the collective behaviors of complex systems composed of many agents entrained to each other and to external events. In this paper, we extend concepts of entrainment to the dynamics of human collective attention. We conducted a detailed investigation of the unfolding of human entrainment - as expressed by the content and patterns of hundreds of thousands of messages on Twitter - during the 2012 US presidential debates. By time locking these data sources, we quantify the impact of the unfolding debate on human attention. We show that collective social behavior covaries second-by-second to the interactional dynamics of the debates: A candidate speaking induces rapid increases in mentions of his name on social media and decreases in mentions of the other candidate. Moreover, interruptions by an interlocutor increase the attention received. We also highlight a distinct time scale for the impact of salient moments in the debate: Mentions in social media start within 5-10 seconds after the moment; peak at approximately one minute; and slowly decay in a consistent fashion across well-known events during the debates. Finally, we show that public attention after an initial burst slowly decays through the course of the debates. Thus we demonstrate that large-scale human entrainment may hold across a number of distinct scales, in an exquisitely time-locked fashion. The methods and results pave the way for careful study of the dynamics and mechanisms of large-scale human entrainment.Comment: 20 pages, 7 figures, 6 tables, 4 supplementary figures. 2nd version revised according to peer reviewers' comments: more detailed explanation of the methods, and grounding of the hypothese

Toward a Digital Twin of a Solid Oxide Fuel Cell Microcogenerator: Data-Driven Modelling

Solid oxide fuel cells (SOFC) could facilitate the green energy transition as they can produce high-temperature heat and electricity while emitting only water when supplied with hydrogen. Additionally, when operated with natural gas, these systems demonstrate higher thermoelectric efficiency compared to traditional microturbines or alternative engines. Within this context, although digitalisation has facilitated the acquisition of extensive data for precise modelling and optimal management of fuel cells, there remains a significant gap in developing digital twins that effectively achieve these objectives in real-world applications. Existing research predominantly focuses on the use of machine learning algorithms to predict the degradation of fuel cell components and to optimally design and theoretically operate these systems. In light of this, the presented study focuses on developing digital twin-oriented models that predict the efficiency of a commercial gas-fed solid oxide fuel cell under various operational conditions. This study uses data gathered from an experimental setup, which was employed to train various machine learning models, including artificial neural networks, random forests, and gradient boosting regressors. Preliminary findings demonstrate that the random forest model excels, achieving an R2 score exceeding 0.98 and a mean squared error of 0.14 in estimating electric efficiency. These outcomes could validate the potential of machine learning algorithms to support fuel cell integration into energy management systems capable of improving efficiency, pushing the transition towards sustainable energy solutions

Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): an overview of their mechanisms of formation

Advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs) have a pathogenetic role in the development and progression of different oxidative-based diseases including diabetes, atherosclerosis, and neurological disorders. AGEs and ALEs represent a quite complex class of compounds that are formed by different mechanisms, by heterogeneous precursors and that can be formed either exogenously or endogenously. There is a wide interest in AGEs and ALEs involving different aspects of research which are essentially focused on set-up and application of analytical strategies (1) to identify, characterize, and quantify AGEs and ALEs in different pathophysiological conditions ; (2) to elucidate the molecular basis of their biological effects ; and (3) to discover compounds able to inhibit AGEs/ALEs damaging effects not only as biological tools aimed at validating AGEs/ALEs as drug target, but also as promising drugs. All the above-mentioned research stages require a clear picture of the chemical formation of AGEs/ALEs but this is not simple, due to the complex and heterogeneous pathways, involving different precursors and mechanisms. In view of this intricate scenario, the aim of the present review is to group the main AGEs and ALEs and to describe, for each of them, the precursors and mechanisms of formation

Effects of simulated altitude (normobaric hypoxia) on cardiorespiratory parameters and circulating endothelial precursors in healthy subjects

<p>Abstract</p> <p>Background</p> <p>Circulating Endothelial Precursors (PB-EPCs) are involved in the maintenance of the endothelial compartment being promptly mobilized after injuries of the vascular endothelium, but the effects of a brief normobaric hypoxia on PB-EPCs in healthy subjects are scarcely studied.</p> <p>Methods</p> <p>Clinical and molecular parameters were investigated in healthy subjects (n = 8) in basal conditions (T0) and after 1 h of normobaric hypoxia (T1), with Inspiratory Fraction of Oxygen set at 11.2% simulating 4850 mt of altitude. Blood samples were obtained at T0 and T1, as well as 7 days after hypoxia (T2).</p> <p>Results</p> <p>In all studied subjects we observed a prompt and significant increase in PB-EPCs, with a return to basal value at T2. The induction of hypoxia was confirmed by Alveolar Oxygen Partial Pressure (PAO₂) and Spot Oxygen Saturation decreases. Heart rate increased, but arterial pressure and respiratory response were unaffected. The change in PB-EPCs percent from T0 to T1 was inversely related to PAO₂at T1. Rapid (T1) increases in serum levels of hepatocyte growth factor and erythropoietin, as well as in cellular PB-EPCs-expression of Hypoxia Inducible Factor-1α were observed.</p> <p>Conclusion</p> <p>In conclusion, the endothelial compartment seems quite responsive to standardized brief hypoxia, possibly important for PB-EPCs activation and recruitment.</p