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Publications in Applied Sciences by NOMIS researchers

Photovoice as a method for co-constructing agroecological knowledge in northern Malawi

NOMIS Researcher(s)

Published in

January 1, 2021

A transdisciplinary project examining agroecological management alternatives in Malawi utilized mixed methods to learn from and about farmer knowledge of biodiversity. Wild biodiversity was assessed on 96 farms within a study area of 16 villages. Forty-two farmers from the 96 farms were involved in the photovoice sub-study discussed here. They received camera training then took photographs of plants and animals that were meaningful to them; subsequently 42 interviews were conducted with farmers to discuss the photos and elicit greater understanding of their perceptions about insects and pest management. Workshops were then utilized to discuss findings, facilitate horizontal knowledge exchange among project stakeholders, and encourage farmers to co-design experiments testing ecological management strategies. The photographs were used in the workshops to expand knowledge about pests and natural enemies. Combining photovoice interviews with workshops and field visits supported a process of co-constructing agroecological knowledge.

Research field(s)
Applied Sciences, Agriculture, Agronomy & Agriculture, Fisheries & Forestry, Agronomy & Agriculture

DOI
10.1080/21683565.2021.1901831

Microwave quantum illumination with a digital phase-conjugated receiver

NOMIS Researcher(s)

Published in

September 21, 2020

Quantum illumination is a sensing technique that employs entangled signal-idler beams to improve the detection efficiency of low-reflectivity objects in environments with large thermal noise. The advantage over classical strategies is evident at low signal brightness, a feature which could make the protocol an ideal prototype for non-invasive scanning or low-power short-range radar. Here we experimentally investigate the concept of quantum illumination at microwave frequencies, by generating entangled fields using a Josephson parametric converter which are then amplified to illuminate a room-temperature object at a distance of 1 meter. Starting from experimental data, we simulate the case of perfect idler photon number detection, which results in a quantum advantage compared to the relative classical benchmark. Our results highlight the opportunities and challenges on the way towards a first room-temperature application of microwave quantum circuits.

Research field(s)
Applied Sciences, Information & Communication Technologies, Networking & Telecommunications

DOI
10.1109/RadarConf2043947.2020.9266397

CRISPR off-target detection with DISCOVER-seq

NOMIS Researcher(s)

Published in

May 1, 2020

DISCOVER-seq (discovery of in situ Cas off-targets and verification by sequencing) is a broadly applicable approach for unbiased CRISPR–Cas off-target identification in cells and tissues. It leverages the recruitment of DNA repair factors to double-strand breaks (DSBs) after genome editing with CRISPR nucleases. Here, we describe a detailed experimental protocol and analysis pipeline with which to perform DISCOVER-seq. The principle of this method is to track the precise recruitment of MRE11 to DSBs by chromatin immunoprecipitation followed by next-generation sequencing. A customized open-source bioinformatics pipeline, BLENDER (blunt end finder), then identifies off-target sequences genome wide. DISCOVER-seq is capable of finding and measuring off-targets in primary cells and in situ. The two main advantages of DISCOVER-seq are (i) low false-positive rates because DNA repair enzyme binding is required for genome edits to occur and (ii) its applicability to a wide variety of systems, including patient-derived cells and animal models. The whole protocol, including the analysis, can be completed within 2 weeks.

Research field(s)
Applied Sciences, Enabling & Strategic Technologies, Bioinformatics

DOI
10.1038/s41596-020-0309-5

Transcriptional and Functional Changes of the Human Microvasculature during Physiological Aging and Alzheimer Disease

NOMIS Researcher(s)

Published in

May 1, 2020

Aging of the circulatory system correlates with the pathogenesis of a large spectrum of diseases. However, it is largely unknown which factors drive the age-dependent or pathological decline of the vasculature and how vascular defects relate to tissue aging. The goal of the study is to design a multianalytical approach to identify how the cellular microenvironment (i.e., fibroblasts) and serum from healthy donors of different ages or Alzheimer disease (AD) patients can modulate the functionality of organ-specific vascular endothelial cells (VECs). Long-living human microvascular networks embedding VECs and fibroblasts from skin biopsies are generated. RNA-seq, secretome analyses, and microfluidic assays demonstrate that fibroblasts from young donors restore the functionality of aged endothelial cells, an effect also achieved by serum from young donors. New biomarkers of vascular aging are validated in human biopsies and it is shown that young serum induces angiopoietin-like-4, which can restore compromised vascular barriers. This strategy is then employed to characterize transcriptional/functional changes induced on the blood–brain barrier by AD serum, demonstrating the importance of PTP4A3 in the regulation of permeability. Features of vascular degeneration during aging and AD are recapitulated, and a tool to identify novel biomarkers that can be exploited to develop future therapeutics modulating vascular function is established.

Research field(s)
Applied Sciences, Enabling & Strategic Technologies, Nanoscience & Nanotechnology

DOI
10.1002/adbi.202000044

Fibroblast Growth Factor 2-Mediated Regulation of Neuronal Exosome Release Depends on VAMP3/Cellubrevin in Hippocampal Neurons

NOMIS Researcher(s)

Published in

March 1, 2020

Extracellular vesicles (EVs) are endogenous membrane-derived vesicles that shuttle bioactive molecules between glia and neurons, thereby promoting neuronal survival and plasticity in the central nervous system (CNS) and contributing to neurodegenerative conditions. Although EVs hold great potential as CNS theranostic nanocarriers, the specific molecular factors that regulate neuronal EV uptake and release are currently unknown. A combination of patch-clamp electrophysiology and pH-sensitive dye imaging is used to examine stimulus-evoked EV release in individual neurons in real time. Whereas spontaneous electrical activity and the application of a high-frequency stimulus induce a slow and prolonged fusion of multivesicular bodies (MVBs) with the plasma membrane (PM) in a subset of cells, the neurotrophic factor basic fibroblast growth factor (bFGF) greatly increases the rate of stimulus-evoked MVB-PM fusion events and, consequently, the abundance of EVs in the culture medium. Proteomic analysis of neuronal EVs demonstrates bFGF increases the abundance of the v-SNARE vesicle-associated membrane protein 3 (VAMP3, cellubrevin) on EVs. Conversely, knocking-down VAMP3 in cultured neurons attenuates the effect of bFGF on EV release. The results determine the temporal characteristics of MVB-PM fusion in hippocampal neurons and reveal a new function for bFGF signaling in controlling neuronal EV release.

Research field(s)
Applied Sciences, Enabling & Strategic Technologies, Nanoscience & Nanotechnology

DOI
10.1002/advs.201902372

Self-serving incentives impair collective decisions by increasing conformity

NOMIS Researcher(s)

Published in

November 1, 2019

The average judgment of large numbers of people has been found to be consistently better than the best individual response. But what motivates individuals when they make collective decisions? While it is a popular belief that individual incentives promote out-of-the-box thinking and diverse solutions, the exact role of motivation and reward in collective intelligence remains unclear. Here we examined collective intelligence in an interactive group estimation task where participants were rewarded for their individual or group’s performance. In addition to examining individual versus collective incentive structures, we controlled whether participants could see social information about the others’ responses. We found that knowledge about others’ responses reduced the wisdom of the crowd and, crucially, this effect depended on how people were rewarded. When rewarded for the accuracy of their individual responses, participants converged to the group mean, increasing social conformity, reducing diversity and thereby diminishing their group wisdom. When rewarded for their collective performance, diversity of opinions and the group wisdom increased. We conclude that the intuitive association between individual incentives and individualist opinion needs revising.

Research field(s)
Applied Sciences, Information & Communication Technologies, Artificial Intelligence & Image Processing

DOI
10.1371/journal.pone.0224725

Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy

NOMIS Researcher(s)

Published in

January 1, 2019

Motivation Multiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full-term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy-related pathologies including preterm birth and preeclampsia. Results We performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net (EN) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified. Availability and implementation Datasets and scripts for reproduction of results are available through: Https://nalab.stanford.edu/multiomics-pregnancy/.

Research field(s)
Applied Sciences, Enabling & Strategic Technologies, Bioinformatics

DOI
10.1093/bioinformatics/bty537

Predicting age from the transcriptome of human dermal fibroblasts

NOMIS Researcher(s)

Published in

December 20, 2018

Biomarkers of aging can be used to assess the health of individuals and to study aging and age-related diseases. We generate a large dataset of genome-wide RNA-seq profiles of human dermal fibroblasts from 133 people aged 1 to 94 years old to test whether signatures of aging are encoded within the transcriptome. We develop an ensemble machine learning method that predicts age to a median error of 4 years, outperforming previous methods used to predict age. The ensemble was further validated by testing it on ten progeria patients, and our method is the only one that predicts accelerated aging in these patients.

Research field(s)
Applied Sciences, Enabling & Strategic Technologies, Bioinformatics

DOI
10.1186/s13059-018-1599-6

Effect of combined systemic and local morpholino treatment on the spinal muscular atrophy δ7 mouse model phenotype

NOMIS Researcher(s)

Published in

March 1, 2014

Background Spinal muscular atrophy (SMA) is a fatal motor neuron disease of childhood that is caused by mutations in the SMN1 gene. Currently, no effective treatment is available. One possible therapeutic approach is the use of antisense oligos (ASOs) to redirect the splicing of the paralogous gene SMN2, thus increasing functional SMN protein production. Various ASOs with different chemical properties are suitable for these applications, including a morpholino oligomer (MO) variant with a particularly excellent safety and efficacy profile. Objective We investigated a 25-nt MO sequence targeting the negative intronic splicing silencer (ISS-N1) 10 to 34 region. Methods We administered a 25-nt MO sequence against the ISS-N1 region of SMN2 (HSMN2Ex7D[-10-34]) in the SMAΔ7 mouse model and evaluated the effect and neuropathologic phenotype. We tested different concentrations (from 2 to 24 nM) and delivery protocols (intracerebroventricular injection, systemic injection, or both). We evaluated the treatment efficacy regarding SMN levels, survival, neuromuscular phenotype, and neuropathologic features. Results We found that a 25-nt MO sequence against the ISS-N1 region of SMN2 (HSMN2Ex7D[-10-34]) exhibited superior efficacy in transgenic SMAΔ7 mice compared with previously described sequences. In our experiments, the combination of local and systemic administration of MO (bare or conjugated to octaguanidine) was the most effective approach for increasing full-length SMN expression, leading to robust improvement in neuropathologic features and survival. Moreover, we found that several small nuclear RNAs were deregulated in SMA mice and that their levels were restored by MO treatment. Conclusion These results indicate that MO-mediated SMA therapy is efficacious and can result in phenotypic rescue, providing important insights for further development of ASO-based therapeutic strategies in SMA patients. © 2014 Elsevier HS Journals, Inc.

Research field(s)
Applied Sciences, Enabling & Strategic Technologies, Optoelectronics & Photonics

DOI
10.1016/j.clinthera.2014.02.004

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