Jonathan Arnold

• PhD Yale University 1982
• Professor (Full) at University of Georgia

The Maximally Informative Next Experiment or MINE is a new experimental design approach for experiments, such as those in omics, in which the number of effects or parameters p greatly exceeds the number of samples n (p > n). Classical experimental design presumes n > p for inference about parameters and its application to p > n can lead to over-fit...

Oil spills are a frequent perturbation to the marine environment that has rapid and significant impacts on the local microbiome. Previous studies have shown that exposure to synthetic dispersant alone did not enhance heterotrophic microbial activity or oxidation rates of specific hydrocarbon components but increased the abundance of some taxa (e.g....

Utilizing a microfluidic chip with serpentine channels, we inoculated the chip with an agar plug with Neurospora crassa mycelium and successfully captured individual hyphae in channels. For the first time, we report the presence of an autonomous clock in hyphae. Fluorescence of a mCherry reporter gene driven by a clock-controlled gene-2 promoter (c...

The presence of Arbuscular Mycorrhizal Fungi (AMF) in vascular land plant roots is one of the most ancient of symbioses supporting nitrogen and phosphorus exchange for photosynthetically derived carbon. Here we provide a multi-scale modeling approach to predict AMF colonization of a worldwide crop from a Recombinant Inbred Line (RIL) population der...

Environmental perturbations shape the structure and function of microbial communities. Oil spills are a major perturbation and resolving spills often requires active measures like dispersant application that can exacerbate the initial disturbance. Species-specific responses of microorganisms to oil and dispersant exposure during such perturbations...

SARS-CoV-2 infection has been associated with increased autoimmune disease risk. Past studies have not aligned regarding the most prevalent autoimmune diseases after infection, however. Furthermore, the relationship between infection severity and new autoimmune disease risk has not been well examined. We used RECOVER’s electronic health record (EHR...

Importance The profile of gastrointestinal (GI) tract outcomes associated with the postacute and chronic phases of COVID-19 in children and adolescents remains unclear. Objective To investigate the risks of GI tract symptoms and disorders during the postacute (28-179 days after documented SARS-CoV-2 infection) and the chronic (180-729 days after d...

Antimicrobial peptides (AMPs) are excellent at fighting many different infections. This demonstrates how important it is to make new AMPs that are even better at eliminating infections. The fundamental transformation in a variety of scientific disciplines, which led to the emergence of machine learning techniques, has presented significant opportun...

Background: Nationally, many ASCVD patients fail to achieve an LDL-C <70 mg/dL, and uptake of both statin and non-statin therapies is low. The degree to which this varies across health systems is less clear. Methods: A cross sectional analysis was performed where lipid levels and lipid lowering therapies (LLT) were assessed using electronic health...

Importance The effect of montelukast in reducing symptom duration among outpatients with mild to moderate COVID-19 is uncertain. Objective To assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19. Design, Setting, and Participants This randomized clinical trial (Accelerating COVID-19...

We investigated the risks of post-acute and chronic adverse kidney outcomes of SARS-CoV-2 infection in the pediatric population via a retrospective cohort study using data from the RECOVER program. We included 1,864,637 children and adolescents under 21 from 19 children’s hospitals and health institutions in the US with at least six months of follo...

Estimating transmission rates is a challenging yet essential aspect of comprehending and controlling the spread of infectious diseases. Various methods exist for estimating transmission rates, each with distinct assumptions, data needs, and constraints. This study introduces a novel phylogenetic approach called transRate, which integrates genetic i...

Accurate reconstruction of species trees often relies on the quality of input gene trees estimated from molecular sequences. Previous studies suggested that if the sequence length is fixed, the maximum likelihood may produce biased gene trees which subsequently mislead inference of species trees. Two key questions need to be answered in this contex...

In-person undergraduate research experiences (UREs) promote students’ integration into careers in life science research. In 2020, the COVID-19 pandemic prompted institutions hosting summer URE programs to offer them remotely, raising questions about whether undergraduates who participate in remote research can experience scientific integration and...

A consensus species tree is reconstructed from 11 gene trees for human, bat, and pangolin beta coronaviruses from samples taken early in the pandemic (prior to April 1, 2020). Using coalescent theory, the shallow (short branches relative to the hosts) consensus species tree provides evidence of recent gene flow events between bat and pangolin beta...

There are quintillions of data on deoxyribonucleic acid (DNA) and protein in publicly accessible data banks, and that number is expanding at an exponential rate. Many scientific fields, such as bioinformatics and drug discovery, rely on such data; nevertheless, gathering and extracting data from these resources is a tough undertaking. This data sho...

There are quintillions of data on deoxyribonucleic acid (DNA) and protein in publicly accessible data banks, and that number is expanding at an exponential rate. Many scientific fields, such as bioinformatics and drug discovery, rely on such data; nevertheless, gathering and extracting data from these resources is a tough undertaking. This data sho...

System biology relies on holistic biomolecule measurements, and untangling biochemical networks requires time-series metabolomics profiling. With current metabolomic approaches, time-series measurements can be taken for hundreds of metabolic features, which decode underlying metabolic regulation. Such a metabolomic dataset is untargeted with most f...

We determined the macroscopic limit for phase synchronization of cellular clocks in an artificial tissue created by a “big chamber” microfluidic device to be about 150,000 cells or less. The dimensions of the microfluidic chamber allowed us to calculate an upper limit on the radius of a hypothesized quorum sensing signal molecule of 13.05 nm using...

Neurospora crassa propagates through dissemination of conidia, which develop through specialized structures called conidiophores. Recent work has identified striking variation in conidiophore morphology, using a wild population collection from Louisiana, United States of America (USA) to classify three distinct phenotypes: Wild-Type (WT), Wrap, and...

Objectives: Empiric segmentation is a rapidly growing, learning health system approach that uses large health care system data sets to identify groups of high-risk patients who may benefit from similar interventions. We aimed to review studies that used data-driven approaches to segment high-risk patient populations and describe how their designs...

In-person undergraduate research experiences (UREs) promote students' integration into careers in life science research. In 2020, the COVID-19 pandemic prompted institutions hosting summer URE programs to offer them remotely, raising questions about whether undergraduates who participate in remote research can experience scientific integration. To...

The COVID-19 pandemic shut down undergraduate research programs across the United States. A group of 23 colleges, universities, and research institutes hosted remote undergraduate research programs in the life sciences during Summer 2020. Given the unprecedented offering of remote programs, we carried out a study to describe and evaluate them. Usin...

With both light entrainment data (L/D) and free running data in the dark (D/D), Variable Topology Ensemble Methods (VTENS) were used to reconstruct the entire genome-scale clock network involving 3380 genes and their products under the hypothesis that clock-controlled genes are both transcriptionally regulated and post-transcriptionally regulated...

Background & Aims Cancer metastasis into distant organs is an evolutionarily selective process. A better understanding of the driving forces endowing proliferative plasticity of tumor seeds in distant soils is required to develop and adapt better treatment systems for this lethal stage of the disease. To this end, we aimed to utilize transcript exp...

We determined the macroscopic limit for phase synchronization of cellular clocks in an artificial tissue created by a “big chamber” microfluidic device to be about 150,000 cells or less. The dimensions of the microfluidic chamber allowed us to calculate an upper limit on the radius of a hypothesized quorum sensing signal of 13.05 nm using a diffusi...

The COVID-19 pandemic shut down undergraduate research programs across the U.S. Twenty-three sites offered remote undergraduate research programs in the life sciences during summer 2020. Given the unprecedented offering of remote research experiences, we carried out a study to describe and evaluate these programs. Using structured templates, we doc...

The vegetative life cycle in the model filamentous fungus, Neurospora crassa, relies on the development of conidiophores to produce new spores. Environmental, temporal, and genetic components of conidiophore development have been well characterized; however, little is known about their morphological variation. We explored conidiophore architectural...

Over 7 million liters of Corexit EC9500A and EC9527A were applied to the Gulf of Mexico in response to the Deepwater Horizon oil spill. The impacts of dispersants remain under debate and negative, positive, and inconclusive impacts have been reported. Here, metatrancriptomics was applied in the context of metapangenomes to microcosms that simulated...

Stochastic networks for the clock were identified by ensemble methods using genetic algorithms that captured the amplitude and period variation in single cell oscillators of Neurospora crassa. The genetic algorithms were at least an order of magnitude faster than ensemble methods using parallel tempering and appeared to provide a globally optimum s...

Stochastic networks for the clock were identified by ensemble methods using genetic algorithms that captured the amplitude and period variation in single cell oscillators of Neurospora crassa. The genetic algorithms were at least an order of magnitude faster than ensemble methods using parallel tempering and appeared to provide a globally optimum s...

Motivation: Time-series NMR has advanced our knowledge about metabolic dynamics. Before analyzing compounds through modeling or statistical methods, chemical features need to be tracked and quantified. However, because of peak overlap and peak shifting, the available protocols are time consuming at best or even impossible for some regions in NMR s...

Four inter-related measures of phase are described to study the phase synchronization of cellular oscillators, and computation of these measures is described and illustrated on single cell fluorescence data from the model filamentous fungus, Neurospora crassa. One of these four measures is the phase shift ϕ in a sinusoid of the form x(t) = A(cos(ωt...

Dense time-series metabolomics data are essential for unraveling the underlying dynamic properties of metabolism. Here we extend high-resolution-magic angle spinning (HR-MAS) to enable continuous in vivo monitoring of metabolism by NMR (CIVM-NMR) and provide analysis tools for these data. First, we reproduced a result in human chronic lymphoid leuk...

Using a microfluidics device, fluorescence of a recorder (mCherry or mVenus) gene driven by a clock-controlled gene-2 promoter ( ccg-2p ) was measured simultaneously on over 1000 single cells of Neurospora crassa every half hour for 10 days under each of varied light and temperature conditions. Single cells were able to entrain to light over a...

Dense time-series metabolomics data are essential for unraveling the underlying dynamic properties of metabolism. Here we extend high-resolution-magic angle spinning (HR-MAS) to enable continuous in vivo monitoring of metabolism by NMR (CIVM-NMR) and provide analysis tools for these data. First, we reproduced a result in human chronic lymphoid leuk...

In previous work we reconstructed the entire transcriptional network for all 2,418 clock-associated genes in the model filamentous fungus, N. crassa. Several authors have suggested that there is extensive post-transcriptional control in the genome-wide clock network (IEEE 3: 27, 2015). Here we have successfully reconstructed the entire clock networ...

A major challenge in systems biology is to infer the parameters of regulatory networks that operate in a noisy environment, such as in a single cell. In a stochastic regime it is hard to distinguish noise from the real signal and to infer the noise contribution to the dynamical behavior. When the genetic network displays oscillatory dynamics, it is...

Summary features of MCMC runs with parallel tempering for the 868 and 1591 single cell data sets. (DOCX)

Bar charts of the parameters from the macroscopic deterministic model (Table 2 in column 3) in blue and single cell stochastic model (Table 2 in column 6) in orange. Parameters are subdivided into: (A) decay rates; (B) transcription and translation rates; (C) interaction parameters between genes and their products on a log scale; (D) initial condit...

Fluoresecent data from a recorder downstream of a ccg-2 promoter from 1591 single cells stored in an excel file. Rows are different times, and columns are different cells. Time points are spaced at half-hour intervals over more than 11 days. (CSV)

Aging and the biological clock are linked via metabolism. We explore how different pathways within metabolism link aging and the clock. These linking pathways include those involving: (1) sphingolipid metabolism; (2) the sir2 complex of genes affecting caloric restriction; (3) pathways underlying oxidative stress; (4) the cell cycle; and (5) glucos...

The lunar cycle has long been suspected to influence biological phenomena. Folklore alludes to such a relationship, but previous scientific analyses have failed to find significant associations. It has been shown that lunar cycles indeed have effects on animals; significant associations between human circadian rhythms and lunar cycles have also bee...

We present a novel growth phenomenon in N. crassa identified using microfluidic technologies. N. crassa cells form a complex web-like network through hyphal extension, branching, and fusion. Our preliminary data indicate that after this filamentous network has been established, bursts of tree-like structures build upon these pre-existing network tr...

SAIL (System for Adaptive Interest-based Learning) is an open-source web based adaptive learning system designed for interdisciplinary instruction. SAIL-SB has the potential to transform education by empowering transdisciplinary knowledge acquisition. This is particularly important in fields that accepts newcomers with diverse scholastic background...

The synchronization of stochastic coupled oscillators is a central problem in physics and an emerging problem in biology, particularly in the context of circadian rhythms. Most measurements on the biological clock are made at the macroscopic level of millions of cells. Here measurements are made on the oscillators in single cells of the model funga...

Using an automated cell counting technique developed previously (Case et al., Ecology and Evolution 2014; 4: 3494), we explore the lifespan effects of lac-1, a ceramide synthase gene paralogous to lag-1 in Neurospora crassa in conjunction with the band bd (ras-1) gene. We find that the replicative lifespan of a lac-1KObd double mutants is short, ab...

A fundamental problem in physics is measuring and modeling the synchronization of coupled stochastic oscillators. The problem is relatively recent in biology, where it has become possible to measure stochastic oscillators in single cells. A variety of synchronization measures have been proposed to describe a field of coupled stochastic oscillators....

RNA regulatory elements play a significant role in gene regulation. Riboswitches, a widespread group of regulatory RNAs, are vital components of many bacterial genomes. These regulatory elements generally function by forming a ligand-induced alternative fold that controls access to ribosome binding sites or other regulatory sites in RNA. Riboswitch...

Most genetic networks, such as that for the biological clock, are part of much larger modules controlling fundamental processes in the cell, such as metabolism, development, and response to environmental signals. For example, the biological clock is part of a much larger network controlling the circadian rhythms of about 2418 distinct genes in the...

Doing large-scale genomics experiments can be expensive, and so experimenters want to get the most information out of each experiment. To this end the Maximally Informative Next Experiment (MINE) criterion for experimental design was developed. Here we explore this idea in a simplified context, the linear model. Four variations of the MINE method f...

The biological clock affects aging through ras-1 (bd) and lag-1, and these two longevity genes together affect a clock phenotype and the clock oscillator in Neurospora crassa. Using an automated cell-counting technique for measuring conidial longevity, we show that the clock-associated genes lag-1 and ras-1 (bd) are true chronological longevity gen...

This paper reports a droplet microfluidic system that is capable of generating droplets, encapsulating cells, incubating cells, and measuring biological clock behavior via fluorescent signals on a large number of single cells simultaneously over a long period of time (∼48 hours).

The developmental adaptation model (Martin & Martin, 2002) provides insights into how current experiences and resources (proximal variables) and past experiences (distal variables) are correlated with outcomes (e.g., well-being) in later life. Applying this model, the current study examined proximal and distal variables associated with positive and...

The adaptive Runge–Kutta (ARK) method on multi-general-purpose graphical processing units (GPUs) is used for solving large nonlinear systems of first-order ordinary differential equations (ODEs) with over ∼10 000 variables describing a large genetic network in systems biology for the biological clock. To carry out the computation of the trajectory...

The adaptive Runge–Kutta (ARK) method on multi-general-purpose graphical processing units (GPUs) is used for solving large nonlinear systems of first-order ordinary differential equations (ODEs) with over ∼10 000 variables describing a large genetic network in systems biology for the biological clock. To carry out the computation of the trajectory...

Objectives: The purpose of this study was to assess the relationship between apolipoprotein E (APOE), life events and engagement, and subjective well-being (as measured by positive and negative affect) among centenarians. Based on the life stress paradigm, we predicted that higher levels of stress would allow APOE to influence positive and negativ...

A new numerical technique to solve nonlinear systems of initial value problems for nonlinear first-order differential equations (ODEs) that model genetic networks in systems biology is developed. This technique is based on finding local Galerkin approximations on each sub-interval at a given time grid of points using piecewise hat functions. Compar...

A new numerical technique to solve nonlinear systems of initial value problems for nonlinear first-order differential equations (ODEs) that model genetic networks in systems biology is developed. This technique is based on finding local Galerkin approximations on each sub-interval at a given time grid of points using piecewise hat functions. Compar...

The goals of this article are to (a) establish the concurrent and clinical validity of the Global Deterioration scale in assessing cognitive functions and stages of dementia among centenarians, (b) identify the prevalence of all-cause dementia in representative samples of centenarians, and (c) demonstrate how variations in sample demographic charac...

We present GKIN, a simulator and a comprehensive graphical interface where one can draw the model specification of reactions between hypothesized molecular participants in a gene regulatory and biochemical reaction network (or genetic network for short). The solver is written in C++ in a nearly platform independent manner to simulate large ensemble...

Regarding the purpose of this study, the researchers analyzed the roles that both life events (life-time positive events and life-time negative events) and personality (Neuroticism, Extraversion, Trust, Competence, and Ideas) played in participants of the Georgia Centenarian Study. The researchers analyzed these variables to determine whether they...

Fatigue is a common and frequently observed complaint among older adults. However, knowledge about the nature and correlates of fatigue in old age is very limited. This study examined the relationship of functional indicators, psychological and situational factors and fatigue for 210 octogenarians and centenarians from the Georgia Centenarian Study...

Leukocyte telomere length is widely considered a biomarker of human age and in many studies indicative of health or disease. We have obtained quantitative estimates of telomere length from blood leukocytes in a population sample, confirming results of previous studies that telomere length significantly decreases with age. Telomere length was also p...

RNA profiles of experiment 1-QA response samples by RNA Nano LabChip (Agilent Technologies, Inc.). The leftmost lane is an RNA ladder with marker sizes indicated in nucleotides. Successive time points are indicated in hrs at the bottom of each lane. (TIFF)

Distribution of residuals from the regression line (in black) after background subtraction and normalization. Gene features with positive residuals are considered above background (see Materials and Methods). Responders are those in the right tail of each distribution shown. In each panel the inset is a normal plot [48] in which observed ranks of r...

KEGG pathway for aromatic amino acid and QA metabolism [53]. Enzymes in red are encoded by QA-responsive genes in Table 3. (TIF)

KEGG pathway for TCA cycle [53]. Enzymes in red are encoded by QA-responsive genes in Table 3. (TIF)

KEGG pathway for glycolysis [53]). Enzymes in red are encoded by QA-responsive genes in Table 3. (TIF)

KEGG pathway for Val, Leu, Ile degradation [53]. Enzymes in red are encoded by QA-responsive genes in Table 3. (TIF)

3 of the 20 give random initial conditions give similar fits as measured by the χ2χ. The remaining 17 random initial conditions do slightly worse. Each of the 20 equilibration runs was done for 35,000 sweeps followed by an accumulation run of 5000 sweeps for a total of 40,000 sweeps. All 20 runs involve a total of 200,000 sweeps. The ensemble with...

KEGG pathway for starch & sucrose metabolism [53]. Enzymes in red are encoded by QA-responsive genes in Table 3. (TIF)

KEGG pathway for butanoate metabolism [53]. Enzymes in red are encoded by QA-responsive genes in Table 3. (TIF)

KEGG pathway for pyruvate metabolism [53]. Enzymes in red are encoded by QA-responsive genes in Table 3. (TIF)

An ensemble of genetic networks that describe how the model fungal system, Neurospora crassa, utilizes quinic acid (QA) as a sole carbon source has been identified previously. A genetic network for QA metabolism involves the genes, qa-1F and qa-1S, that encode a transcriptional activator and repressor, respectively and structural genes, qa-2, qa-3,...