Large scale physiological readjustment during growth enables rapid, comprehensive and inexpensive systems analysis

Abstract Background Rapidly characterizing the operational interrelationships among all genes in a given organism is a critical bottleneck to significantly advancing our understanding of thousands of newly sequenced microbial and eukaryotic species. While evolving technologies for global profiling of transcripts, proteins, and metabolites are making it possible to comprehensively survey cellular physiology in newly sequenced organisms, these experimental techniques have not kept pace with sequencing efforts. Compounding these technological challenges is the fact that individual experiments typically only stimulate relatively small-scale cellular responses, thus requiring numerous expensive experiments to survey the operational relationships among nearly all genetic elements. Therefore, a relatively quick and inexpensive strategy for observing changes in large fractions of the genetic elements is highly desirable. Results We have discovered in the model organism Halobacterium salinarum NRC-1 that batch culturing in complex medium stimulates meaningful changes in the expression of approximately two thirds of all genes. While the majority of these changes occur during transition from rapid exponential growth to the stationary phase, several transient physiological states were detected beyond what has been previously observed. In sum, integrated analysis of transcript and metabolite changes has helped uncover growth phase-associated physiologies, operational interrelationships among two thirds of all genes, specialized functions for gene family members, waves of transcription factor activities, and growth phase associated cell morphology control. Conclusions Simple laboratory culturing in complex medium can be enormously informative regarding the activities of and interrelationships among a large fraction of all genes in an organism. This also yields important baseline physiological context for designing specific perturbation experiments at different phases of growth. The integration of such growth and perturbation studies with measurements of associated environmental factor changes is a practical and economical route for the elucidation of comprehensive systems-level models of biological systems

Niche adaptation by expansion and reprogramming of general transcription factors

Experimental analysis of TFB family proteins in a halophilic archaeon reveals complex environment-dependent fitness contributions. Gene conversion events among these proteins can generate novel niche adaptation capabilities, a process that may have contributed to archaeal adaptation to extreme environments

Selective Translation of Low Abundance and Upregulated Transcripts in Halobacterium salinarum.

When organisms encounter an unfavorable environment, they transition to a physiologically distinct, quiescent state wherein abundant transcripts from the previous active growth state continue to persist, albeit their active transcription is downregulated. In order to generate proteins for the new quiescent physiological state, we hypothesized that the translation machinery must selectively translate upregulated transcripts in an intracellular milieu crowded with considerably higher abundance transcripts from the previous active growth state. Here, we have analyzed genome-wide changes in the transcriptome (RNA sequencing [RNA-seq]), changes in translational regulation and efficiency by ribosome profiling across all transcripts (ribosome profiling [Ribo-seq]), and protein level changes in assembled ribosomal proteins (sequential window acquisition of all theoretical mass spectra [SWATH-MS]) to investigate the interplay of transcriptional and translational regulation in Halobacterium salinarum as it transitions from active growth to quiescence. We have discovered that interplay of regulatory processes at different levels of information processing generates condition-specific ribosomal complexes to translate preferentially pools of low abundance and upregulated transcripts. Through analysis of the gene regulatory network architecture of H. salinarum, Escherichia coli, and Saccharomyces cerevisiae, we demonstrate that this conditional, modular organization of regulatory programs governing translational systems is a generalized feature across all domains of life.IMPORTANCE Our findings demonstrate conclusively that low abundance and upregulated transcripts are preferentially translated, potentially by environment-specific translation systems with distinct ribosomal protein composition. We show that a complex interplay of transcriptional and posttranscriptional regulation underlies the conditional and modular regulatory programs that generate ribosomes of distinct protein composition. The modular regulation of ribosomal proteins with other transcription, translation, and metabolic genes is generalizable to bacterial and eukaryotic microbes. These findings are relevant to how microorganisms adapt to unfavorable environments when they transition from active growth to quiescence by generating proteins from upregulated transcripts that are in considerably lower abundance relative to transcripts associated with the previous physiological state. Selective translation of transcripts by distinct ribosomes could form the basis for adaptive evolution to new environments through a modular regulation of the translational systems

A workflow for genome-wide mapping of archaeal transcription factors with ChIP-seq

Deciphering the structure of gene regulatory networks across the tree of life remains one of the major challenges in postgenomic biology. We present a novel ChIP-seq workflow for the archaea using the model organism Halobacterium salinarum sp. NRC-1 and demonstrate its application for mapping the genome-wide binding sites of natively expressed transcription factors. This end-to-end pipeline is the first protocol for ChIP-seq in archaea, with methods and tools for each stage from gene tagging to data analysis and biological discovery. Genome-wide binding sites for transcription factors with many binding sites (TfbD) are identified with sensitivity, while retaining specificity in the identification the smaller regulons (bacteriorhodopsin-activator protein). Chromosomal tagging of target proteins with a compact epitope facilitates a standardized and cost-effective workflow that is compatible with high-throughput immunoprecipitation of natively expressed transcription factors. The Pique package, an open-source bioinformatics method, is presented for identification of binding events. Relative to ChIP-Chip and qPCR, this workflow offers a robust catalog of protein–DNA binding events with improved spatial resolution and significantly decreased cost. While this study focuses on the application of ChIP-seq in H. salinarum sp. NRC-1, our workflow can also be adapted for use in other archaea and bacteria with basic genetic tools

Utilizing new technologies to measure therapy effectiveness for mental and physical health

Mental health is quickly becoming a major policy concern, with recent data reporting increasing and disproportionately worse mental health outcomes, including anxiety, depression, increased substance abuse, and elevated suicidal ideation. One specific population that is especially high risk for these issues is the military community because military conflict, deployment stressors, and combat exposure contribute to the risk of mental health problems. Although several pharmacological approaches have been employed to combat this epidemic, their efficacy is mixed at best, which has led to novel nonpharmacological approaches. One such approach is Operation Surf, a nonprofit that provides nature-based programs advocating the restorative power of the ocean and surfing. Although the limited research in this area has shown a positive impact on the health of veterans, these results were based on self-reported survey instruments that suffer from a series of well-known biases. Fortunately, the recent introduction of wearable technology (e.g., Whoop bands) that unobtrusively gather physiological data such as heart rate variability (HRV), resting heart rate (RHR), and both rapid eye movement (REM) and deep sleep, offers an opportunity to validate or invalidate traditional survey assessment data. This study used survey data to measure changes in depression, anxiety, and posttraumatic stress disorder (PTSD), together with data generated from Whoop bands, and qualitative data, producing a more robust set of programmatic efficacy inferences for military veterans who participated in Operation Surf between 2021–2022. Paired samples t tests were used to analyze the data gathered before the intervention, immediately after, and 1 month later. Survey scores before the therapy, as measured by the psychometrically sound PHQ-8 (depression), PCL-5 (PTSD), and GAD-7 (anxiety), were significantly higher than both time points after therapy, revealing statistically significant and clinically significant decreases in anxiety, depression, and PTSD symptoms. Physiological data indicated varying degrees of statistically significant change in HRV, RHR, REM sleep, and deep sleep, while the qualitative data provided supported the quantitative findings. Taken together, the introduction of physiological data gathered from wearable technology can hopefully further understanding toward a low-cost, scalable treatment modality while eliminating stigmas and barriers to care for military veterans and informing public policy care decisions

Future Work

The Industrial Revolution. The Digital Age. These revolutions radically altered the workplace and society. We may be on the cusp of a new era—one that will rival or even surpass these historic disruptions. Technology such as artificial intelligence, robotics, virtual reality, and cutting-edge monitoring devices are developing at a rapid pace. These technologies have already begun to infiltrate the workplace and will continue to do so at ever increasing speed and breadth.This Article addresses the impact of these emerging technologies on the workplace of the present and the future. Drawing upon interviews with leading technologists, the Article explains the basics of these technologies, describes their current applications in the workplace, and predicts how they are likely to develop in the future. It then examines the legal and policy issues implicated by the adoption of technology in the workplace—most notably job losses, employee classification, privacy intrusions, discrimination, safety and health, and impacts on disabled workers. These changes will surely strain a workplace regulatory system that is ill-equipped to handle them. What is unclear is whether the strain will be so great that the system breaks, resulting in a new paradigm of work.Whether or not we are on the brink of a workplace revolution or a more modest evolution, emerging technology will exacerbate the inadequacies of our current workplace laws. This Article discusses possible legislative and judicial reforms designed to ameliorate these problems and stave off the possibility of a collapse that would leave a critical mass of workers without any meaningful protection, power, or voice. The most far-reaching of these options is a proposed “Law of Work” that would address the wide-ranging and interrelated issues posed by these new technologies via a centralized regulatory scheme. This proposal, as well as other more narrowly focused reforms, highlight the major impacts of technology on our workplace laws, underscore both the current and future shortcomings of those laws, and serve as a foundation for further research and discussion on the future of work

New and improved demonstrations, each illustrating a single scientific paper

Thesis (Ed.M.)--Boston Universit

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 122, December 1973

This special bibliography lists 343 reports, articles, and other documents introduced into the NASA scientific and technical information system in November 1973

Hot Transcriptomics

DNA microarray technology allows for a quick and easy comparison of complete transcriptomes, resulting in improved molecular insight in fluctuations of gene expression. After emergence of the microarray technology about a decade ago, the technique has now matured and has become routine in many molecular biology laboratories. Numerous studies have been performed that have provided global transcription patterns of many organisms under a wide range of conditions. Initially, implementation of this high-throughput technology has lead to high expectations for ground breaking discoveries. Here an evaluation is performed of the insight that transcriptome analysis has brought about in the field of hyperthermophilic archaea. The examples that will be discussed have been selected on the basis of their impact, in terms of either biological insight or technological progress