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Article ; Online: Random-Reaction-Seed Method for Automated Identification of Neurite Elongation and Branching

Alvason Zhenhua Li / Lawrence Corey / Jia Zhu

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 10

Abstract: Abstract Conventional deterministic algorithms (i.e., skeletonization and edge-detection) lack robustness and sensitivity to reliably detect the neurite elongation and branching of low signal-to-noise-ratio microscopy images. Neurite outgrowth ... ...

Abstract	Abstract Conventional deterministic algorithms (i.e., skeletonization and edge-detection) lack robustness and sensitivity to reliably detect the neurite elongation and branching of low signal-to-noise-ratio microscopy images. Neurite outgrowth experiments produce an enormous number of images that require automated measurement; however, the tracking of neurites is easily lost in the automated process due to the intrinsic variability of neurites (either axon or dendrite) under stimuli. We have developed a stochastic random-reaction-seed (RRS) method to identify neurite elongation and branching accurately and automatically. The random-seeding algorithm of RRS is based on the hidden-Markov-model (HMM) to offer a robust enough way for tracing arbitrary neurite structures, while the reaction-seeding algorithm of RRS secures the efficiency of random seeding. It is noteworthy that RRS is capable of tracing a whole neurite branch by only one initial seed, so that RRS is proficient at quantifying extensive amounts of neurite outgrowth images with noisy background in microfluidic devices of biomedical engineering fields. The method also showed notable performance for reconstructing of net-like structures, and thus is expected to be proficient for biomedical feature extractions in a wide range of applications, such as retinal vessel segmentation and cell membrane profiling in spurious-edge-tissues.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Author Correction

Karsten Eichholz / Alvason Zhenhua Li / Kurt Diem / Michael Claus Jensen / Jia Zhu / Lawrence Corey

Scientific Reports, Vol 11, Iss 1, Pp 1-

A CAR RNA FISH assay to study functional and spatial heterogeneity of chimeric antigen receptor T cells in tissue

2021 Volume 3

Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A CAR RNA FISH assay to study functional and spatial heterogeneity of chimeric antigen receptor T cells in tissue

Karsten Eichholz / Alvason Zhenhua Li / Kurt Diem / Michael Claus Jensen / Jia Zhu / Lawrence Corey

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 13

Abstract: Abstract Chimeric antigen receptor (CAR) T cells are engineered cells used in cancer therapy and are studied to treat infectious diseases. Trafficking and persistence of CAR T cells is an important requirement for efficacy to target cancer. Here, we ... ...

Abstract	Abstract Chimeric antigen receptor (CAR) T cells are engineered cells used in cancer therapy and are studied to treat infectious diseases. Trafficking and persistence of CAR T cells is an important requirement for efficacy to target cancer. Here, we describe a CAR RNA FISH histo-cytometry platform combined with a random reaction seed image analysis algorithm to quantitate spatial distribution and in vivo functional activity of a CAR T cell population at a single cell resolution for preclinical models. In situ, CAR T cell exhibited a heterogenous effector gene expression and this was related to the distance from tumor cells, allowing a quantitative assessment of the potential in vivo effectiveness. The platform offers the potential to study immune functions of genetically engineered cells in situ with their target cells in tissues with high statistical power and thus, can serve as an important tool for preclinical assessment of CAR T cell effectiveness.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Nuclear Factor kappa B is required for the production of infectious human herpesvirus 8 virions

NeginNBlattman / LawrenceCorey

Frontiers in Microbiology, Vol

2014 Volume 5

Abstract: Human herpesvirus 8 (HHV8) infection leads to potent activation of nuclear factor kappa B (NFB) in primary and transformed cells. We used recombinant HHV8 (rKSHV.219) expressing green fluorescent protein under the constitutive cellular promoter ... ...

Abstract	Human herpesvirus 8 (HHV8) infection leads to potent activation of nuclear factor kappa B (NFB) in primary and transformed cells. We used recombinant HHV8 (rKSHV.219) expressing green fluorescent protein under the constitutive cellular promoter elongation factor 2 and red fluorescent protein under an early HHV8 lytic gene promoter T1.1, to monitor replication during infection of human foreskin fibroblasts (HF), noting changes in NFB activity. In primary HF, NFB levels do not affect HHV8 ability to establish infection or maintain latency. Furthermore, there was no effect on the percent of cells undergoing reactivation from latency, and there were similar numbers of released and cell associated HHV8 viral particles following reactivation in the presence of inhibitors. Reactivation of HHV8 in latently infected HF in the presence of NFB inhibitors resulted in production of viral particles that did not efficiently establish infection, due to deficiencies in binding and/or entry into normally permissive cells. Exogenous expression of glycoprotein M, an envelope protein involved in viral binding and entry was able to partially overcome the deficiency induced by NFB inhibitors. Our data indicate that in primary cells, NFB is not required for infection, establishment of latency, or entry into the lytic cycle, but is required for the expression of virion associated genes involved in the initial steps of virion infectivity. These studies suggest that strategies to inhibit NFB may prevent HHV8 spread and should be considered as a potential therapeutic target for preventing HHV8 associated diseases.
Keywords	KSHV ; hf ; NFκB ; HHV8 ; MVEC ; BCBL-1 ; Microbiology ; QR1-502 ; Science ; Q
Subject code	570
Language	English
Publishing date	2014-04-01T00:00:00Z
Publisher	Frontiers
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Evidence for non-steady-state carbon emissions from snow-scoured alpine tundra.

Knowles, John F / Blanken, Peter D / Lawrence, Corey R / Williams, Mark W

Nature communications

2019 Volume 10, Issue 1, Page(s) 1306

Abstract: High-latitude warming is capable of accelerating permafrost degradation and the decomposition of previously frozen carbon. The existence of an analogous high-altitude feedback, however, has yet to be directly evaluated. We address this knowledge gap by ... ...

Abstract	High-latitude warming is capable of accelerating permafrost degradation and the decomposition of previously frozen carbon. The existence of an analogous high-altitude feedback, however, has yet to be directly evaluated. We address this knowledge gap by coupling a radiocarbon-based model to 7 years (2008-2014) of continuous eddy covariance data from a snow-scoured alpine tundra meadow in Colorado, USA, where solifluction lobes are associated with discontinuous permafrost. On average, the ecosystem was a net annual source of 232 ± 54 g C m
Language	English
Publishing date	2019-03-21
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-019-09149-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Meeting report

Maurine D. Miner / Linda-Gail Bekker / Tamara Kredo / Niresh Bhagwandin / Lawrence Corey / Glenda E. Gray

Trials, Vol 22, Iss 1, Pp 1-

South African Medical Research Council Standard of Care in Clinical Research in Low- And Middle-Income Settings Summit, November 2017

2021 Volume 8

Abstract: Abstract A cornerstone of HIV prevention clinical trials is providing a combination prevention package to all trial participants. The elements included in that standard of care (SoC) package evolve as new prevention modalities are developed. Pre-exposure ...

Abstract	Abstract A cornerstone of HIV prevention clinical trials is providing a combination prevention package to all trial participants. The elements included in that standard of care (SoC) package evolve as new prevention modalities are developed. Pre-exposure prophylaxis (PrEP) was recommended by the World Health Organization for persons at high risk of acquiring HIV, but not all countries immediately adopted those recommendations. The South African Medical Research Council (SAMRC) convened a summit to discuss issues relating to SoC and PrEP in HIV prevention clinical trials taking place in lower- to middle-income countries (LMIC). Policymakers, regulators, ethicists, experts in law, researchers, representatives of advocacy groups, and the HIV Vaccine Trials Network (HVTN) presented a framework within which SoC principles could be articulated. A group of subject matter experts presented on the regulatory, ethical, scientific, and historic framework of SoC in clinical trials, focusing on PrEP in South Africa. Summit participants discussed how and when to include new HIV treatment and prevention practices into existing clinical guidelines and trial protocols, as well as the opportunities for and challenges to scaling up interventions. The summit addressed challenges to PrEP provision, such as inconsistent efficacy amongst different populations and various biological, virological, and immunological explanations for this heterogeneity. Advocates and community members propagated the urgent need for accessible interventions that could avert HIV infection. The meeting recommended supporting access to PrEP in HIV prevention trials by (1) developing PrEP access plans for HIV vaccine trials, (2) creating a PrEP fund that would supply PrEP to sites conducting HIV prevention trials via a central procurement mechanism, and (3) supporting the safety monitoring of PrEP. This report summarizes the presentations and discussions from the summit in order to highlight the importance of SoC in HIV prevention clinical trials.
Keywords	Pre-exposure prophylaxis ; South Africa ; Standard of care ; LMIC ; HIV/AIDS ; Clinical trials ; Medicine (General) ; R5-920
Subject code	360
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The trajectory of soil development and its relationship to soil carbon dynamics

Lawrence, Corey R. / Schulz, Marjorie S. / Masiello, Caroline A. / Chadwick, Oliver A. / Harden, Jennifer W.

Geoderma. 2021 Dec. 01, v. 403

2021

Abstract: It has been postulated that the amount of soil organic carbon (SOC) associated with soil minerals exhibits a threshold relationship in response to effective soil moisture (estimated as precipitation less evapotranspiration). To better characterize the ... ...

Abstract	It has been postulated that the amount of soil organic carbon (SOC) associated with soil minerals exhibits a threshold relationship in response to effective soil moisture (estimated as precipitation less evapotranspiration). To better characterize the role of moisture in influencing mechanisms of SOC storage during pedogenesis, we compare soils from two different chronosequence sites: the Santa Cruz and Mattole River marine terraces that together form a soil age-by-climate gradient (i.e., climo-chronosequence). Our results demonstrate how variation in the effective soil moisture may drive soil development along divergent pedogenic trajectories, resulting in variations in the form and depth distribution of secondary weathering products. In particular, the residual metals Fe and Al are directly related to the type of secondary minerals that accumulate during weathering, and these variations are coupled to differences in the storage and long-term preservation of SOC both within and between soils. Over time, these differences in soil development may lead to ‘pedogenic thresholds’ that further differentiate soil characteristics and influence SOC dynamics. In this case, the pedogenic threshold takes the form of clay-rich argillic horizons that once formed, inhibit aqueous transport, decouple shallow and deep soil environments, and potentially limit SOC inputs and increase microbial recycling in deep soils. Our data suggest argillic horizon development is favorable in the drier Santa Cruz soils, where kaolinite is the dominant secondary weathering product. In contrast, greater available moisture in soils of the Mattole chronosequence drive a different weathering trajectory characterized by the accumulation of more amorphous secondary minerals. As a result, the Mattole soils and do not exhibit argillic horizon development but are instead characterized by greater accumulation of SOC across all depths sampled. Overall, our results illustrate how the interaction of climate (i.e., moisture) and time may shape the trajectory of soil development and the dynamics of SOC storage and preservation.
Keywords	argillic horizons ; carbon sequestration ; chronosequences ; climate ; evapotranspiration ; kaolinite ; rivers ; soil formation ; soil organic carbon ; soil water
Language	English
Dates of publication	2021-1201
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	281080-3
ISSN	1872-6259 ; 0016-7061
ISSN (online)	1872-6259
ISSN	0016-7061
DOI	10.1016/j.geoderma.2021.115378
Database	NAL-Catalogue (AGRICOLA)

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Article: The influence of soil development on the depth distribution and structure of soil microbial communities

Leewis, Mary-Cathrine / Lawrence, Corey R. / Schulz, Marjorie S. / Tfaily, Malak M. / Ayala-Ortiz, Christian Orlando / Flores, Gilberto E. / Mackelprang, Rachel / McFarland, Jack W.

Soil biology & biochemistry. 2022 Aug. 16,

2022

Abstract: Although it has been shown that the interaction of climate and time shape the dynamics of soil organic matter (SOM) storage and preservation in soil, the role of soil microbial communities in this dynamic remains unclear. Microbial communities are ... ...

Abstract	Although it has been shown that the interaction of climate and time shape the dynamics of soil organic matter (SOM) storage and preservation in soil, the role of soil microbial communities in this dynamic remains unclear. Microbial communities are present throughout soil profiles and likely play critical roles in SOM and nutrient cycling, however the influence of other factors such as soil development (i.e., age) and the composition SOM on microbial community variation with depth has yet to be quantified. Improving our understanding of the relationship between soil development, soil depth, and microbial communities may provide insight to the critical role they play in cycling and preservation of SOM, as well as more mechanistic predictions of the response of soil communities to change, such as landscape-scale changes in available moisture or temperature regimes. Here we compare soils spanning a soil age by climate gradient (i.e., climo-chronosequence) to better understand the mechanisms which influence soil microbial community structure and the molecular composition of SOM. While we observed little depth-dependence in metrics of microbial community structure (i.e., composition, diversity, dissimilarity) across the range of soil development under a wetter climate, we found significant depth-dependent changes in community metrics under a drier climate, which became more pronounced as soils became older. This shift in bacterial and archaeal community structure and diversity is most apparent below a clay-rich argillic horizon formed in the older, drier soils. The molecular composition of SOM as measured by high resolution mass spectrometry (i.e., FTICR MS) also exhibited similar shifts in composition with soil depth and age. Our results highlight how soil moisture shapes the interaction of soil development, SOM, and microbial community composition. Differences in the moisture regime between our two study sites drive differences in biogeochemical depth gradients and subsequent variation in soil microbes and SOM. This suggests that knowledge of not just the pedogenic trajectory of soil development, but also the spatial position relative to distinct pedogenic features, are important for explaining variations in the depth-dependencies of microbial communities and associated SOM.
Keywords	Archaea ; age of soil ; argillic horizons ; biochemistry ; climate ; community structure ; mass spectrometry ; microbial communities ; soil depth ; soil microorganisms ; soil organic matter ; soil water ; temperature
Language	English
Dates of publication	2022-0816
Publishing place	Elsevier Ltd
Document type	Article
Note	Pre-press version
ZDB-ID	280810-9
ISSN	0038-0717
ISSN	0038-0717
DOI	10.1016/j.soilbio.2022.108808
Database	NAL-Catalogue (AGRICOLA)

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Article: Mechanisms for retention of low molecular weight organic carbon varies with soil depth at a coastal prairie ecosystem

McFarland, Jack W. / Lawrence, Corey R. / Creamer, Courtney / Schulz, Marjorie S. / Conaway, Christopher H. / Peek, Sara / Waldrop, Mark P. / Sevilgen, Sabrina / Haw, Monica

Soil biology & biochemistry. 2022 May, v. 168

2022

Abstract: Though primary sources of carbon (C) to soil are plant inputs (e.g., rhizodeposits), the role of microorganisms as mediators of soil organic carbon (SOC) retention is increasingly recognized. Yet, insufficient knowledge of sub-soil processes complicates ... ...

Abstract	Though primary sources of carbon (C) to soil are plant inputs (e.g., rhizodeposits), the role of microorganisms as mediators of soil organic carbon (SOC) retention is increasingly recognized. Yet, insufficient knowledge of sub-soil processes complicates attempts to describe microbial-driven C cycling at depth as most studies of microbial-mineral-C interactions focus on surface horizons. We leveraged a well-studied paleo-marine terrace (90 ka) located near Santa Cruz, CA, to characterize the short-term (days to weeks) and intermediate-term (months to years) fate of two low molecular weight organic carbon. compounds at three depths in the soil profile (∼25 cm, A horizon; ∼75 cm A/B transition; and ∼125 cm, B horizon). We employed isotopically-labeled glucose (GLU) and oxalic acid (OXA) to represent two common classes of rhizodeposits: carbohydrates and organic acids. Using a combination of laboratory (9 d) and field (490 d) incubations, we traced the fate of GLU-C and OXA-C through dissolved-, metal-associated-, and microbially-respired CO₂ and bulk SOC pools. Our results suggest new SOC retention (i.e., defined as ¹³C label identified in solid or aqueous fractions) over intermediate time frames (490 d) is correlated with patterns in short-term (9 d) cycling dynamics, which in turn is related to the theoretical efficiency by which microorganisms process each substrate. For all horizons (A, A/B, and B) GLU-C was converted to CO₂ more quickly than OXA-C with modeled decomposition rates ∼2–4 times faster for GLU depending on microbial density (higher in A than B horizon). The faster decomposition rates of GLU-C increased fractional recovery (0.399 ± 0.026 to 0.504 ± 0.030 for GLU-C) compared to OXA-C (0.035 ± 0.003 to 0.127 ± 0.010) among all horizons in our field experiment (490 d). Though the overall proportion of GLU-C recovered in solid fractions did not vary significantly with horizon, based on ¹³C recovered in aqueous fractions the apparent mechanism for retention did. After the 9-d laboratory incubation, fractional recovery for GLU-C among C pools associated with microbial biomass was almost 20× higher than OXA-C (0.192 versus 0.010, respectively across all horizons). More than a year later, 43–46% of GLU-C retained in the field incubation was extractable with a neutral salt (representing a pool of soil C residing within or available to microbial biomass) among A and A/B horizons, while only 6% of retained GLU-C was similarly extractable in the B horizon. Thus, it appears among depths with higher microbial density (A, A/B horizons), anabolic recycling is the most likely process contributing to the persistence of glucose C, whereas abiotic sinks contributed more to intermediate-term stability for GLU-C in the B horizon. By contrast, most OXA-C was lost, presumably as CO₂, over the short-term from the A and A/B horizons (fractional recovery: 0.136 ± 0.011 and 0.091 ± 0.002, respectively). However, though substantially lower than GLU-C recovered at the conclusion of our field experiment, the fraction of oxalic acid C retained in the B horizon over both short- (0.72 ± 0.037) and intermediate-time (0.127 ± 0.010) frames was several-fold higher than for overlying horizons. The specific process(es) (e.g., more efficient microbial utilization, metal-organic complexation, direct adsorption to the mineral matrix, etc.) contributing to higher retention for OXA-C at depth are discussed but remain unresolved.
Keywords	B horizons ; adsorption ; carbon dioxide ; ecosystems ; field experimentation ; glucose ; isotope labeling ; microbial biomass ; molecular weight ; oxalic acid ; soil depth ; soil organic carbon ; soil profiles ; subsoil
Language	English
Dates of publication	2022-05
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	280810-9
ISSN	0038-0717
ISSN	0038-0717
DOI	10.1016/j.soilbio.2022.108601
Database	NAL-Catalogue (AGRICOLA)

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Article: A sequential selective dissolution method to quantify storage and stability of organic carbon associated with Al and Fe hydroxide phases

Heckman, Katherine / Harden, Jennifer W / Lawrence, Corey R

Geoderma. 2017,

2017

Abstract: Stabilization of SOM (soil organic matter) is regulated in part by sorption and desorption reactions happening at mineral surfaces, as well as precipitation and dissolution of organo-metal complexes. Fe and Al hydroxides play a particularly significant ... ...

Abstract	Stabilization of SOM (soil organic matter) is regulated in part by sorption and desorption reactions happening at mineral surfaces, as well as precipitation and dissolution of organo-metal complexes. Fe and Al hydroxides play a particularly significant role in SOM stabilization in soils due to their ubiquitous distribution and their highly reactive surface properties. Iron and Al hydroxides exist in soils across a wide spectrum of crystallinity, ranging from dissolved Fe and Al cations which combine with organics to form organo-metal precipitates to the more crystalline end members, goethite and gibbsite, which sorb SOM through a variety of molecular interactions. Though the importance of these sorption and precipitation reactions has long been recognized, the distribution of SOM among Fe and Al hydroxides of differing crystallinity has not been well quantified, nor has the timescale over which these stabilization mechanisms operate. In an attempt to measure the distribution of organic C among (i) Al- and Fe-humus complexes (ii) short-range-order (SRO) Al and Fe hydroxide surfaces and (iii) crystalline Fe oxyhydroxide surfaces, a single method combining several selective mineral dissolutions was applied to soils of four different geneses (a tropical forest Andisol, a temperate forest basaltic Mollisol, a Mediterranean coastal prairie Mollisol, and a northern mixed hardwood forest Spodosol). The traditional reactants used in selective dissolutions were replaced with carbon-free analogues so that the carbon released along with the Fe and Al at each stage of the selective dissolution process could be measured. Selective dissolutions were performed sequentially: Na-pyrophosphate (organo-Al and Fe complexes) followed by hydroxylamine (SRO Al and Fe hydroxides) followed by dithionite-HCl (crystalline Fe hydroxides). Carbon, Al, and Fe concentrations, as well as radiocarbon abundance were measured in the solutions yielded by each stage of the selective dissolution process. Results suggest that precipitation of organo-metal complexes (Na-pyrophosphate extractable C) often accounts for the largest pool of stabilized C among the three selectively dissolved pools, but these complexes were 14C enriched in comparison to C from the other selectively dissolved pools and the residual C left on crystalline mineral surfaces after all three stages of selective dissolution. Hydroxylamine and dithionite-HCl extractable C pools were, on average, small and often below detection level in temperate soils. However, radiocarbon values for these C pools were generally depleted in comparison to other pools. These results suggest variation in organo-mineral complex stability is associated with degree of crystallinity of the mineral phase. Overall, this work suggests that sequential selective dissolution methods are a promising tool for characterizing the content and isotopic composition of soil C associated with distinct organo-mineral and organo-metal associations.
Keywords	aluminum ; Andisols ; carbon sinks ; cations ; crystal structure ; desorption ; gibbsite ; goethite ; hardwood forests ; hydroxides ; hydroxylamine ; iron ; iron oxyhydroxides ; Mollisols ; organic carbon ; soil organic matter ; Spodosols ; temperate forests ; temperate soils ; tropical forests
Language	English
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ZDB-ID	281080-3
ISSN	1872-6259 ; 0016-7061
ISSN (online)	1872-6259
ISSN	0016-7061
DOI	10.1016/j.geoderma.2017.09.043
Database	NAL-Catalogue (AGRICOLA)

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