scholarly journals Multiplex recording of cellular events over time on CRISPR biological tape

Science ◽  
2017 ◽  
Vol 358 (6369) ◽  
pp. 1457-1461 ◽  
Author(s):  
Ravi U. Sheth ◽  
Sung Sun Yim ◽  
Felix L. Wu ◽  
Harris H. Wang
Keyword(s):  
Cell Population ◽  
Large Scale ◽  
Environmental Changes ◽  
Biological Information ◽  
Cellular Events ◽  
Biological Signals ◽  
A Cell ◽  
Temporal Measurement ◽  
New Applications ◽  
Over Time

Although dynamics underlie many biological processes, our ability to robustly and accurately profile time-varying biological signals and regulatory programs remains limited. Here we describe a framework for storing temporal biological information directly in the genomes of a cell population. We developed a “biological tape recorder” in which biological signals trigger intracellular DNA production that is then recorded by the CRISPR-Cas adaptation system. This approach enables stable recording over multiple days and accurate reconstruction of temporal and lineage information by sequencing CRISPR arrays. We further demonstrate a multiplexing strategy to simultaneously record the temporal availability of three metabolites (copper, trehalose, and fucose) in the environment of a cell population over time. This work enables the temporal measurement of dynamic cellular states and environmental changes and suggests new applications for chronicling biological events on a large scale.

scholarly journals A molecular calcium integrator reveals a striatal cell-type driving aversion

2020 ◽  
Author(s):  
Christina K. Kim ◽  
Mateo I. Sanchez ◽  
Paul Hoerbelt ◽  
Lief E. Fenno ◽  
Robert C. Malenka ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Large Scale ◽  
Calcium Concentration ◽  
Modular Design ◽  
Cell Type ◽  
Neural Ensembles ◽  
Cellular Events ◽  
Large Scale Analysis ◽  
Genetic Tagging ◽  
A Cell

SUMMARYThe ability to record transient cellular events in the DNA or RNA of cells would enable precise, large-scale analysis, selection, and reprogramming of heterogeneous cell populations. Here we report a molecular technology for stable genetic tagging of cells that exhibit activity-related increases in intracellular calcium concentration (FLiCRE). We used FLiCRE to transcriptionally label activated neural ensembles in the nucleus accumbens of the mouse brain during brief stimulation of aversive inputs. Using single-cell RNA sequencing, we detected FLiCRE transcripts among the endogenous transcriptome, providing simultaneous readout of both cell-type and calcium activation history. We identified a cell-type in the nucleus accumbens activated downstream of long-range excitatory projections. Taking advantage of FLiCRE’s modular design, we expressed an optogenetic channel selectively in this cell-type, and showed that direct recruitment of this otherwise genetically-inaccessible population elicits behavioral aversion. The specificity and minute-resolution of FLiCRE enables molecularly-informed characterization, manipulation, and reprogramming of activated cellular ensembles.

scholarly journals hRUV: Hierarchical approach to removal of unwanted variation for large-scale metabolomics data

2020 ◽  
Author(s):  
Taiyun Kim ◽  
Owen Tang ◽  
Stephen T Vernon ◽  
Katharine A Kott ◽  
Yen Chin Koay ◽  
...  
Keyword(s):  
Biological Sample ◽  
Large Scale ◽  
Large Population ◽  
Plasma Samples ◽  
Hierarchical Approach ◽  
Liquid Chromatography Mass Spectrometry ◽  
Metabolomics Data ◽  
Biological Signals ◽  
Technical Factors ◽  
Over Time

AbstractLiquid chromatography-mass spectrometry based metabolomics studies are increasingly applied to large population cohorts, running for several weeks to months, even extending to years of data acquisition. This inevitably introduces unwanted intra- and inter-batch variations over time that can overshadow true biological signals and thus hinder potential biological discoveries. To date, normalization approaches have struggled to mitigate the variability introduced by technical factors whilst preserving biological variance, especially for protracted acquisitions. Here, we designed an experiment with an arrangement to embed biological sample replicates to measure the variance within and between batches for over 1,000 human plasma samples run over 44 days. We integrate these replicates in a novel workflow to remove unwanted variation in a hierarchical structure (hRUV) by progressively merging the adjustments in neighbouring batches. We demonstrate significant improvement of hRUV over existing methods in maintaining biological signals whilst removing unwanted variation for large scale metabolomics studies.

scholarly journals Lysine Methylation of Non-Histone Proteins

2015 ◽  
pp. 1-2
Author(s):  
Byron Baron
Keyword(s):  
Protein Structure ◽  
Large Scale ◽  
Structure And Function ◽  
Cellular Biology ◽  
Lysine Methylation ◽  
Post Translational Modifications ◽  
A Cell ◽  
And Function ◽  
Small Chemical ◽  
Over Time

Proteomics, or the large-scale study of protein structure and function, has contributed greatly to our understanding of cellular biology and disease. Over time, it has become apparent that the proteome is spatially, temporally, and chemically dynamic allowing for the same protein to perform very different functions and fufill completely unrelated roles in a cell through small chemical changes. This can be described as epiproteomics (just as epigenetic are changes to DNA not encoded in the DNA sequence) and mainly covers Post-Translational Modifications (PTMs) such as phosphorylation, ubiquitination, acetylation or methylation, among over 200 or more.

scholarly journals Analysis of 220 Years of Floodplain Population Dynamics in the US at Different Spatial Scales

Water ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 141
Author(s):  
Firoza Akhter ◽  
Maurizio Mazzoleni ◽  
Luigia Brandimarte
Keyword(s):  
Population Dynamics ◽  
Large Scale ◽  
Spatial Scales ◽  
National Level ◽  
State Level ◽  
Economic Activities ◽  
Protection Measures ◽  
Management Planning ◽  
The Us ◽  
Over Time

In this study, we explore the long-term trends of floodplain population dynamics at different spatial scales in the contiguous United States (U.S.). We exploit different types of datasets from 1790–2010—i.e., decadal spatial distribution for the population density in the US, global floodplains dataset, large-scale data of flood occurrence and damage, and structural and nonstructural flood protection measures for the US. At the national level, we found that the population initially settled down within the floodplains and then spread across its territory over time. At the state level, we observed that flood damages and national protection measures might have contributed to a learning effect, which in turn, shaped the floodplain population dynamics over time. Finally, at the county level, other socio-economic factors such as local flood insurances, economic activities, and socio-political context may predominantly influence the dynamics. Our study shows that different influencing factors affect floodplain population dynamics at different spatial scales. These facts are crucial for a reliable development and implementation of flood risk management planning.

scholarly journals Impact of the municipal merger on watershed management: a study of Lake Kasumigaura, Japan

2021 ◽  
Author(s):  
Takeshi Mizunoya ◽  
Noriko Nozaki ◽  
Rajeev Kumar Singh
Keyword(s):  
Watershed Management ◽  
Large Scale ◽  
Environmental Changes ◽  
Water Environment ◽  
Reduction Rate ◽  
Oxygen Demand ◽  
Policy Implications ◽  
Pollution Reduction ◽  
Lake Kasumigaura ◽  
The Impact

AbstractIn the early 2000s, Japan instituted the Great Heisei Consolidation, a national strategy to promote large-scale municipal mergers. This study analyzes the impact that this strategy could have on watershed management. We select the Lake Kasumigaura Basin, the second largest lake in Japan, for the case study and construct a dynamic expanded input–output model to simulate the ecological system around the Lake, the socio-environmental changes over the period, and their mutual dependency for the period 2012–2020. In the model, we regulate and control the following water pollutants: total nitrogen, total phosphorus, and chemical oxygen demand. The results show that a trade-off between economic activity and the environment can be avoided within a specific range of pollution reduction, given that the prefectural government implements optimal water environment policies, assuming that other factors constraining economic growth exist. Additionally, municipal mergers are found to significantly reduce the budget required to improve the water environment, but merger budget efficiency varies nonlinearly with the reduction rate. Furthermore, despite the increase in financial efficiency from the merger, the efficiency of installing domestic wastewater treatment systems decreases drastically beyond a certain pollution reduction level and eventually reaches a limit. Further reductions require direct regulatory instruments in addition to economic policies, along with limiting the output of each industry. Most studies on municipal mergers apply a political, administrative, or financial perspective; few evaluate the quantitative impact of municipal mergers on the environment and environmental policy implications. This study addresses these gaps.

scholarly journals China’s Investments in Germany and the Impact of the COVID-19 Pandemic

2021 ◽  
Vol 56 (2) ◽  
pp. 113-119
Author(s):  
Xinming Xia ◽  
Wan-Hsin Liu
Keyword(s):  
Large Scale ◽  
Know How ◽  
Advanced Technologies ◽  
The Future ◽  
Potential Impact ◽  
Chinese State ◽  
The Impact ◽  
Gain Access ◽  
Over Time

AbstractThis paper analyses how China’s investments in Germany have developed over time and the potential impact of the COVID-19 pandemic in this regard, based on four different datasets, including our own survey in mid-2020. Our analysis shows that Germany is currently one of the most attractive investment destinations for Chinese investors. Chinese state-owned enterprises have played an important role as investors in Germany — particularly in large-scale projects. The COVID-19 pandemic has had some negative but rather temporary effects on Chinese investments in Germany. Germany is expected to stay attractive to Chinese investors who seek to gain access to advanced technologies and know-how in the future.

Pioneers in International Administration: A Prosopography of the Directors of the League of Nations Secretariat

2019 ◽  
Vol 13 (2) ◽  
pp. 190-227 ◽  
Author(s):  
Torsten Kahlert
Keyword(s):  
International Organizations ◽  
Large Scale ◽  
Second World War ◽  
League Of Nations ◽  
World War ◽  
Clear Trend ◽  
Organizational Contexts ◽  
Career Trajectories ◽  
Second World ◽  
Over Time

AbstractThis article investigates interwar internationalism from the perspective of the highest personnel of the first large-scale international administration, the League of Nations Secretariat. It applies a prosopographical approach in order to map out the development of the composition of the group of the section directors of the Secretariat over time in terms of its social and cultural characteristics and career trajectories. The analysis of gender, age, nationality, as well as educational and professional backgrounds and careers after their service for the League’s Secretariat gives insight on how this group changed over time and what it tells us about interwar internationalism. I have three key findings to offer in this article: First, the Secretariat was far from being a static organization. On the contrary, the Secretariat’s directors developed in three generations each with distinct characteristics. Second, my analysis demonstrates a clear trend towards professionalization and growing maturity of the administration over time. Third, the careers of the directors show a clear pattern of continuity across the Second World War and beyond. Even though the careers continued in different organizational contexts, the majority of the directors remained closely connected to the world of internationalism of the League, the UN world and its surrounding organizations. On a methodological level, the article offers an example of how prosopographical analysis can be used to study international organizations.

A Framework and Case Study for Earthquake Vulnerability Assessment of Incrementally Expanding Buildings

2017 ◽  
Vol 33 (4) ◽  
pp. 1369-1384 ◽  
Author(s):  
David Lallemant ◽  
Henry Burton ◽  
Luis Ceferino ◽  
Zach Bullock ◽  
Anne Kiremidjian
Keyword(s):  
Large Scale ◽  
Building Construction ◽  
Risk Assessment Models ◽  
Earthquake Vulnerability ◽  
Valley Area ◽  
Common Understanding ◽  
Dynamic Structural Analysis ◽  
Neighborhood Level ◽  
Over Time

This study proposes a framework for incorporating time-dependent fragility into large-scale risk assessment models, focusing on incremental building expansion as a significant driver of changes in vulnerability. In rapidly urbanizing areas in developing countries, the pay-as-you-go process of informal building construction and staged expansion is the de facto pattern of growth. While there is a common understanding that such expansions increase the earthquake vulnerability of buildings, this study proposes a framework to model and quantify this increase. Vulnerability curves are developed through incremental dynamic structural analysis for common building expansion typologies. Building expansions are modeled as Markov chain processes and used to simulate stochastic expansion sequences over a building's lifetime. The model is then used to simulate a hypothetical neighborhood in the Kathmandu valley area to understand neighborhood-level risk over time. The study provides a new methodology to analyze changing seismic risk over time, driven by any building modification that impacts the building's vulnerability (incremental expansion, deterioration, retrofit, etc.).

scholarly journals Rapid Spread of the SARS-CoV-2 Variant of Concern 202012/01 in Southern Italy (December 2020–March 2021)

2021 ◽  
Vol 18 (9) ◽  
pp. 4766
Author(s):  
Daniela Loconsole ◽  
Francesca Centrone ◽  
Caterina Morcavallo ◽  
Silvia Campanella ◽  
Anna Sallustio ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Large Scale ◽  
Southern Italy ◽  
Whole Genome ◽  
Third Wave ◽  
Gene Target ◽  
The Third ◽  
Rapid Spread ◽  
Pharmaceutical Interventions ◽  
Over Time

Epidemiological and virological studies have revealed that SARS-CoV-2 variants of concern (VOCs) are emerging globally, including in Europe. The aim of this study was to evaluate the spread of B.1.1.7-lineage SARS-CoV-2 in southern Italy from December 2020–March 2021 through the detection of the S gene target failure (SGTF), which could be considered a robust proxy of VOC B.1.1.7. SGTF was assessed on 3075 samples from week 52/2020 to week 10/2021. A subset of positive samples identified in the Apulia region during the study period was subjected to whole-genome sequencing (WGS). A descriptive and statistical analysis of the demographic and clinical characteristics of cases according to SGTF status was performed. Overall, 20.2% of samples showed SGTF; 155 strains were confirmed as VOC 202012/01 by WGS. The proportion of SGTF-positive samples rapidly increased over time, reaching 69.2% in week 10/2021. SGTF-positive cases were more likely to be symptomatic and to result in hospitalization (p < 0.0001). Despite the implementation of large-scale non-pharmaceutical interventions (NPIs), such as the closure of schools and local lockdowns, a rapid spread of VOC 202012/01 was observed in southern Italy. Strengthened NPIs and rapid vaccine deployment, first among priority groups and then among the general population, are crucial both to contain the spread of VOC 202012/01 and to flatten the curve of the third wave.

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