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UFGI publication round-up week 3/19

Sci Rep. 2018 Mar 22;8(1):5039. doi: 10.1038/s41598-018-23436-w.

Loss of IDH2 Accelerates Age-related Hearing Loss in Male Mice.

Author information

1
Department of Aging and Geriatric Research, University of Florida, Gainesville, Florida, 32610, United States.
2
Center for Hearing and Deafness, State University of New York at Buffalo, New York, 14214, United States.
3
Whitney Laboratory, University of Florida, St Augustine, Florida, 32080, United States.
4
Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, 32610, United States.
5
Department of Applied Biological Chemistry, University of Tokyo, Yayoi, Tokyo, 113, Japan.
6
Department of Aging and Geriatric Research, University of Florida, Gainesville, Florida, 32610, United States. someya@ufl.edu.

Abstract

Isocitrate dehydrogenase (IDH) 2 participates in the TCA cycle and catalyzes the conversion of isocitrate to α-ketoglutarate and NADP+ to NADPH. In the mitochondria, IDH2 also plays a key role in protecting mitochondrial components from oxidative stress by supplying NADPH to both glutathione reductase (GSR) and thioredoxin reductase 2 (TXNRD2). Here, we report that loss of Idh2 accelerates age-related hearing loss, the most common form of hearing impairment, in male mice. This was accompanied by increased oxidative DNA damage, increased apoptotic cell death, and profound loss of spiral ganglion neurons and hair cells in the cochlea of 24-month-old Idh2-/- mice. In young male mice, loss of Idh2 resulted in decreased NADPH redox state and decreased activity of TXNRD2 in the mitochondria of the inner ear. In HEI-OC1 mouse inner ear cell lines, knockdown of Idh2 resulted in a decline in cell viability and mitochondrial oxygen consumption. This was accompanied by decreased NADPH redox state and decreased activity of TXNRD2 in the mitochondria of the HEI-OC1 cells. Therefore, IDH2 functions as the principal source of NADPH for the mitochondrial thioredoxin antioxidant defense and plays an essential role in protecting hair cells and neurons against oxidative stress in the cochlea of male mice.

 

 

Nat Rev Genet. 2018 Mar 21. doi: 10.1038/s41576-018-0002-5. [Epub ahead of print]

The genetics of fruit flavour preferences.

Author information

1
University of Florida, Horticultural Sciences, Gainesville, FL, USA. hjklee@ufl.edu.
2
University of Florida, Horticultural Sciences, Gainesville, FL, USA.

Abstract

Intensively bred fruit crops, including tomatoes and strawberries, are widely viewed as lacking flavour. The lack of breeder focus on the consumer is largely due to the genetic complexity of the flavour phenotype as well as a lack of a simple assay that can define consumer preferences. Rapid advances in genomics have opened up new opportunities to understand the chemistry and genetics of flavour. Here, we describe the underlying causes for the loss of flavour in fruits over time and delineate a blueprint for defining the chemistry of consumer liking, reducing that knowledge into a molecular roadmap for flavour improvement.

 

 

Rheumatology (Oxford). 2018 Mar 19. doi: 10.1093/rheumatology/key052. [Epub ahead of print]

The subgingival microbiome in patients with established rheumatoid arthritis.

Author information

1
Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, USA.
2
Medicine, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA.
3
Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA.
4
Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA.
5
Department of Medicine, College of Medicine, University of Florida, USA.
6
Medicine, North Florida/South Georgia Veterans Health System, USA.
7
Department of Biostatistics, College of Public Health & Health Professions College of Medicine, University of Florida, Gainesville, FL, USA.
8
Department of Surgical Specialties, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE, USA.

Abstract

OBJECTIVES:

To profile and compare the subgingival microbiome of RA patients with OA controls.

METHODS:

RA (n = 260) and OA (n = 296) patients underwent full-mouth examination and subgingival samples were collected. Bacterial DNA was profiled using 16 S rRNA Illumina sequencing. Following data filtering and normalization, hierarchical clustering analysis was used to group samples. Multivariable regression was used to examine associations of patient factors with membership in the two largest clusters. Differential abundance between RA and OA was examined using voom method and linear modelling with empirical Bayes moderation (Linear Models for Microarray Analysis, limma), accounting for the effects of periodontitis, race, marital status and smoking.

RESULTS:

Alpha diversity indices were similar in RA and OA after accounting for periodontitis. After filtering, 286 taxa were available for analysis. Samples grouped into one of seven clusters with membership sizes of 324, 223, 3, 2, 2, 1 and 1 patients, respectively. RA-OA status was not associated with cluster membership. Factors associated with cluster 1 (vs 2) membership included periodontitis, smoking, marital status and Caucasian race. Accounting for periodontitis, 10 taxa (3.5% of those examined) were in lower abundance in RA than OA. There were no associations between lower abundance taxa or other select taxa examined with RA autoantibody concentrations.

CONCLUSION:

Leveraging data from a large case-control study and accounting for multiple factors known to influence oral health status, results from this study failed to identify a subgingival microbial fingerprint that could reliably discriminate RA from OA patients.

 

 

Cancer Biol Ther. 2018 Mar 21:1-32. doi: 10.1080/15384047.2018.1449612. [Epub ahead of print]

UFH-001 cells: A novel triple negative, CAIX-positive, human breast cancer model system.

Author information

1
a Department of Biochemistry and Molecular Biology , Gainesville , FL 32610.
2
b Department of Medicine , University of Florida , Gainesville , FL 32610.
3
c Department of Biology , University of Louisville , Louisville , KY 40292.

Abstract

Human cell lines are an important resource for research, and are often used as in vitro models of human diseases. In response to the mandate that all cells should be authenticated, we discovered that the MDA-MB-231 cells that were in use in our lab, did not validate based on the alleles of 9 different markers (STR Profile). We had been using this line as a model of triple negative breast cancer (TNBC) that has the ability to form tumors in immuno-compromised mice. Based on marker analysis, these cells most closely resembled the MCF10A line, which are a near diploid and normal mammary epithelial line. Yet, the original cells express carbonic anhydrase IX (CAIX) both constitutively and in response to hypoxia and are features that likely drive the aggressive nature of these cells. Thus, we sought to sub-purify CAIX-expressing cells using Fluorescence Activated Cell Sorting (FACS). These studies have revealed a new line of cells that we have name UFH-001, which have the TNBC phenotype, are positive for CAIX expression, both constitutively and in response to hypoxia, and behave aggressively in vivo. These cells may be useful for exploring mechanisms that underlie progression, migration, and metastasis of this phenotype. In addition, constitutive expression of CAIX allows its evaluation as a therapeutic target, both in vivo and in vitro.

 

 

PLoS One. 2018 Mar 19;13(3):e0194283. doi: 10.1371/journal.pone.0194283. eCollection 2018.

Skeletal muscle magnetic resonance biomarkers correlate with function and sentinel events in Duchenne muscular dystrophy.

Abstract

OBJECTIVE:

To provide evidence for quantitative magnetic resonance (qMR) biomarkers in Duchenne muscular dystrophy by investigating the relationship between qMR measures of lower extremity muscle pathology and functional endpoints in a large ambulatory cohort using a multicenter study design.

METHODS:

MR spectroscopy and quantitative imaging were implemented to measure intramuscular fat fraction and the transverse magnetization relaxation time constant (T2) in lower extremity muscles of 136 participants with Duchenne muscular dystrophy. Measures were collected at 554 visits over 48 months at one of three imaging sites. Fat fraction was measured in the soleus and vastus lateralis using MR spectroscopy, while T2 was assessed using MRI in eight lower extremity muscles. Ambulatory function was measured using the 10m walk/run, climb four stairs, supine to stand, and six minute walk tests.

RESULTS:

Significant correlations were found between all qMR and functional measures. Vastus lateralis qMR measures correlated most strongly to functional endpoints (|ρ| = 0.68-0.78), although measures in other rapidly progressing muscles including the biceps femoris (|ρ| = 0.63-0.73) and peroneals (|ρ| = 0.59-0.72) also showed strong correlations. Quantitative MR biomarkers were excellent indicators of loss of functional ability and correlated with qualitative measures of function. A VL FF of 0.40 was an approximate lower threshold of muscle pathology associated with loss of ambulation.

DISCUSSION:

Lower extremity qMR biomarkers have a robust relationship to clinically meaningful measures of ambulatory function in Duchenne muscular dystrophy. These results provide strong supporting evidence for qMR biomarkers and set the stage for their potential use as surrogate outcomes in clinical trials.

 

 

Proc Natl Acad Sci U S A. 2018 Mar 20;115(12):E2839-E2848. doi: 10.1073/pnas.1720662115. Epub 2018 Mar 5.

BEST1 gene therapy corrects a diffuse retina-wide microdetachment modulated by light exposure.

Author information

1
Division of Experimental Retinal Therapies, Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104; karinag@vet.upenn.edu cideciya@pennmedicine.upenn.edu.
2
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; karinag@vet.upenn.edu cideciya@pennmedicine.upenn.edu.
3
Division of Experimental Retinal Therapies, Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
4
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824.
5
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
6
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
7
Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, FL 32611.
8
Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, Toronto, ON M5G 2L3, Canada.

Abstract

Mutations in the BEST1 gene cause detachment of the retina and degeneration of photoreceptor (PR) cells due to a primary channelopathy in the neighboring retinal pigment epithelium (RPE) cells. The pathophysiology of the interaction between RPE and PR cells preceding the formation of retinal detachment remains not well-understood. Our studies of molecular pathology in the canine BEST1 disease model revealed retina-wide abnormalities at the RPE-PR interface associated with defects in the RPE microvillar ensheathment and a cone PR-associated insoluble interphotoreceptor matrix. In vivo imaging demonstrated a retina-wide RPE-PR microdetachment, which contracted with dark adaptation and expanded upon exposure to a moderate intensity of light. Subretinal BEST1 gene augmentation therapy using adeno-associated virus 2 reversed not only clinically detectable subretinal lesions but also the diffuse microdetachments. Immunohistochemical analyses showed correction of the structural alterations at the RPE-PR interface in areas with BEST1 transgene expression. Successful treatment effects were demonstrated in three different canine BEST1 genotypes with vector titers in the 0.1-to-5E11 vector genomes per mL range. Patients with biallelic BEST1 mutations exhibited large regions of retinal lamination defects, severe PR sensitivity loss, and slowing of the retinoid cycle. Human translation of canine BEST1 gene therapy success in reversal of macro- and microdetachments through restoration of cytoarchitecture at the RPE-PR interface has promise to result in improved visual function and prevent disease progression in patients affected with bestrophinopathies.

 

 

Appl Environ Microbiol. 2018 Mar 19;84(7). pii: e02222-17. doi: 10.1128/AEM.02222-17. Print 2018 Apr 1.

Methanogens Are Major Contributors to Nitrogen Fixation in Soils of the Florida Everglades.

Author information

1
Soil and Water Sciences Department, University of Florida, Gainesville, Florida, USA.
2
Earth, Ocean, and Atmospheric Science, Florida State University, Tallahassee, Florida, USA.
3
Soil and Water Sciences Department, University of Florida, Gainesville, Florida, USA aogram@ufl.edu.

Abstract

The objective of this study was to investigate the interaction of the nitrogen (N) cycle with methane production in the Florida Everglades, a large freshwater wetland. This study provides an initial analysis of the distribution and expression of N-cycling genes in Water Conservation Area 2A (WCA-2A), a section of the marsh that underwent phosphorus (P) loading for many years due to runoff from upstream agricultural activities. The elevated P resulted in increased primary productivity and an N limitation in P-enriched areas. Results from quantitative real-time PCR (qPCR) analyses indicated that the N cycle in WCA-2A was dominated by nifH and nirK/S, with an increasing trend in copy numbers in P-impacted sites. Many nifH sequences (6 to 44% of the total) and nifH transcript sequences (2 to 49%) clustered with the methanogenic Euryarchaeota, in stark contrast to the proportion of core gene sequences representing Archaea (≤0.27% of SSU rRNA genes) for the WCA-2A microbiota. Notably, archaeal nifH gene transcripts were detected at all sites and comprised a significant proportion of total nifH transcripts obtained from the unimpacted site, indicating that methanogens are actively fixing N2 Laboratory incubations with soils taken from WCA-2A produced nifH transcripts with the production of methane from H2 plus CO2 and acetate as electron donors and carbon sources. Methanogenic N2 fixation is likely to be an important, although largely unrecognized, route through which fixed nitrogen enters the anoxic soils of the Everglades and may have significant relevance regarding methane production in wetlands.IMPORTANCE Wetlands are the most important natural sources of the greenhouse gas methane, and much of that methane emanates from (sub)tropical peatlands. Primary productivity in these peatlands is frequently limited by the availability of nitrogen or phosphorus; however, the response to nutrient limitations of microbial communities that control biogeochemical cycling critical to ecosystem function may be complex and may be associated with a range of processes, including methane production. We show that many, if not most, of the methanogens in the peatlands of the Florida Everglades possess the nifH gene and actively express it for N2 fixation coupled with methanogenesis. These findings indicate that archaeal N2 fixation would play crucial role in methane emissions and overall N cycle in subtropical wetlands suffering N limitation.

 

 

J Exp Biol. 2018 Mar 19;221(Pt 6). pii: jeb167825. doi: 10.1242/jeb.167825.

Hormetic benefits of prior anoxia exposure in buffering anoxia stress in a soil-pupating insect.

Author information

1
Evolutionary Ecology and Genetics Group, Biodiversity Research Centre, Earth and Life Institute, Université catholique de Louvain, Croix du Sud 4-5, 1348 Louvain-la-Neuve, Belgium.
2
Department of Entomology and Nematology, College of Agriculture and Life Sciences, University of Florida, Gainesville, FL 32611, USA.
3
Department of Integrative Biology, University of California, Berkeley, CA 94720, USA.
4
Department of Entomology and Nematology, College of Agriculture and Life Sciences, University of Florida, Gainesville, FL 32611, USA gclopez@nmsu.edu.
5
Department of Biology, New Mexico State University, Las Cruces, NM 88003, USA.

Abstract

Oxygen is essential for most animals, and exposure to a complete lack of oxygen, i.e. anoxia, can result in irreparable damage to cells that can extend up to the organismal level to negatively affect performance. Although it is known that brief anoxia exposure may confer cross-tolerance to other stressors, few data exist on the biochemical and organismal consequences of repeated intermittent bouts of anoxia exposure. In nature, the Caribbean fruit fly, Anastrepha suspensa (Diptera: Tephritidae), is frequently exposed to heavy tropical rainfall while pupating in the soil, equating to multiple exposures to hypoxia or anoxia during development. Here, we tested whether prior anoxia exposures during pupal development can induce a beneficial acclimation response, and we explored the consequences of prior exposure for both whole-organism performance and correlated biochemical metrics. Pharate adults (the last developmental stage in the pupal case) were most sensitive to anoxia exposure, showing decreased survival and fertility compared with controls. These negative impacts were ameliorated by exposure to anoxia in earlier pupal developmental stages, indicating a hormetic effect of prior anoxia exposure. Anoxia exposure early in pupal development reduced the oxygen debt repaid after anoxia exposure relative to pharate adults experiencing anoxia for the first time. Lipid levels were highest in all pupal stages when exposed to prior anoxia. Prior anoxia thus benefits organismal performance and relocates resources towards lipid storage throughout pupal-adult development.

 

 

J Proteomics. 2018 Mar 20;175:114-126. doi: 10.1016/j.jprot.2018.01.002. Epub 2018 Jan 9.

Quantitative proteomics reveals a role of JAZ7 in plant defense response to Pseudomonas syringae DC3000.

Abstract

Jasmonate ZIM-domain (JAZ) proteins are key transcriptional repressors regulating various biological processes. Although many studies have studied JAZ proteins by genetic and biochemical analyses, little is known about JAZ7-associated global protein networks and how JAZ7 contributes to bacterial pathogen defense. In this study, we aim to fill this knowledge gap by conducting unbiased large-scale quantitative proteomics using tandem mass tags (TMT). We compared the proteomes of a JAZ7 knock-out line, a JAZ7 overexpression line, as well as the wild type Arabidopsis plants in the presence and absence of Pseudomonas syringae DC3000 infection. Both pairwise comparison and multi-factor analysis of variance reveal that differential proteins are enriched in biological processes such as primary and secondary metabolism, redox regulation, and response to stress. The differential regulation in these pathways may account for the alterations in plant size, redox homeostasis and accumulation of glucosinolates. In addition, possible interplay between genotype and environment is suggested as the abundance of seven proteins is influenced by the interaction of the two factors. Collectively, we demonstrate a role of JAZ7 in pathogen defense and provide a list of proteins that are uniquely responsive to genetic disruption, pathogen infection, or the interaction between genotypes and environmental factors.

SIGNIFICANCE:

We report proteomic changes as a result of genetic perturbation of JAZ7, and the contribution of JAZ7 in plant immunity. Specifically, the similarity between the proteomes of a JAZ7 knockout mutant and the wild type plants confirmed the functional redundancy of JAZs. In contrast, JAZ7 overexpression plants were much different, and proteomic analysis of the JAZ7 overexpression plants under Pst DC3000 infection revealed that JAZ7 may regulate plant immunity via ROS modulation, energy balance and glucosinolate biosynthesis. Multiple variate analysis for this two-factor proteomics experiment suggests that protein abundance is determined by genotype, environment and the interaction between them.

 

 

Clin Infect Dis. 2018 Mar 19;66(7):1120-1121. doi: 10.1093/cid/cix968.

Evidence for Mother-to-Child Transmission of Zika Virus Through Breast Milk.

Author information

1
Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville.
2
Emerging Pathogens Institute, University of Florida, Gainesville.
3
Infectious Diseases Research Incubator and the Zoonosis and Emerging Pathogens Regional Collaborative Network, Universidad Centroccidental Lisandro Alvarado, Lara, Venezuela.
4
Health Sciences Department, College of Medicine, Universidad Centroccidental Lisandro Alvarado, Lara, Venezuela.
5
Policlínica Barquisimeto, Lara, Venezuela.
6
Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville.
7
Bioinfoexperts LLC, Thibodaux, Louisiana.
8
Public Health and Infection Research Group, Faculty of Health Sciences, Universidad Tecnológica de Pereira, Colombia.
9
Department of Internal Medicine, Division of Infectious Diseases and Global Medicine, Department of Medicine, College of Medicine, University of Florida, Gainesville.
10
DST-NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), Stellenbosch, South Africa.
11
Department of Infectious Diseases and Tropical Medicine, Instituto Diagnóstico Barquisimeto, IDB Biomedical Research Institute, Lara, Barquisimeto, Venezuela.

Abstract

Zikavirus (ZIKV) is an emerging viral pathogen that continues to spread throughout different regions of the world. Herein we report a case that provides further evidence that ZIKV transmission can occur through breastfeeding by providing a detailed clinical, genomic, and virological case-based description.

 

 

NOTE: These abstracts were retrieved from the U.S. National Library of Medicine website managed in collaboration with the U.S. National Library of Medicine

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