Publications by authors named "Lloyd K"

930 Publications

Duodenal intraepithelial lymphocytosis in Helicobacter pylori gastritis: comparison before and after treatment.

Virchows Arch 2021 Apr 6;478(4):805-809. Epub 2020 Oct 6.

Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, 1959 NE Pacific Street, NE140D, Box 356100, Seattle, WA, 98195-6100, USA.

Our aims were to assess performance of duodenal intraepithelial lymphocyte counting for diagnosis of Helicobacter pylori (H. pylori) gastritis, and effects of eradication therapy on intraepithelial lymphocytosis. Paired duodenal and gastric biopsies from subjects with a pathologic diagnosis of H. pylori gastritis were reviewed. Higher duodenal intraepithelial lymphocyte counts were observed in 40 subjects with H. pylori gastritis (26 ± 5 per villus) than 52 subjects negative for H. pylori (12 ± 2 per villus). After successful eradication therapy, duodenal lymphocytes were indistinguishable from H. pylori-negative subjects, whereas they remained elevated after failed eradication therapy. This study confirms previous reports of increased duodenal intraepithelial lymphocytes in patients with concurrent Helicobacter pylori gastritis. Intraepithelial lymphocyte counts of > 15 per villus or > 10 per 100 enterocytes were predictive of infection. Duodenal lymphocytosis decreases significantly after successful eradication therapy but remains elevated when treatment fails.
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http://dx.doi.org/10.1007/s00428-020-02941-2DOI Listing
April 2021

Time as a microbial resource.

Authors:
Karen G Lloyd

Environ Microbiol Rep 2021 Feb 13;13(1):18-21. Epub 2020 Oct 13.

Microbiology Department, University of Tennessee, Mossman Building Rm 307, Knoxville, TN, 37996, USA.

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http://dx.doi.org/10.1111/1758-2229.12892DOI Listing
February 2021

Time as a microbial resource.

Authors:
Karen G Lloyd

Environ Microbiol Rep 2021 Feb 13;13(1):18-21. Epub 2020 Oct 13.

Microbiology Department, University of Tennessee, Mossman Building Rm 307, Knoxville, TN, 37996, USA.

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http://dx.doi.org/10.1111/1758-2229.12892DOI Listing
February 2021

Using systems medicine to identify a therapeutic agent with potential for repurposing in inflammatory bowel disease.

Dis Model Mech 2020 11 27;13(11). Epub 2020 Nov 27.

Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool L69 3GE, UK

Inflammatory bowel diseases (IBDs) cause significant morbidity and mortality. Aberrant NF-κB signalling is strongly associated with these conditions, and several established drugs influence the NF-κB signalling network to exert their effect. This study aimed to identify drugs that alter NF-κB signalling and could be repositioned for use in IBD. The SysmedIBD Consortium established a novel drug-repurposing pipeline based on a combination of drug discovery and biological assays targeted at demonstrating an impact on NF-κB signalling, and a murine model of IBD. The drug discovery algorithm identified several drugs already established in IBD, including corticosteroids. The highest-ranked drug was the macrolide antibiotic clarithromycin, which has previously been reported to have anti-inflammatory effects in aseptic conditions. The effects of clarithromycin effects were validated in several experiments: it influenced NF-κB-mediated transcription in murine peritoneal macrophages and intestinal enteroids; it suppressed NF-κB protein shuttling in murine reporter enteroids; it suppressed NF-κB (p65) DNA binding in the small intestine of mice exposed to lipopolysaccharide; and it reduced the severity of dextran sulphate sodium-induced colitis in C57BL/6 mice. Clarithromycin also suppressed NF-κB (p65) nuclear translocation in human intestinal enteroids. These findings demonstrate that drug repositioning algorithms can viably be allied to laboratory validation assays in the context of IBD, and that further clinical assessment of clarithromycin in the management of IBD is required.This article has an associated First Person interview with the joint first authors of the paper.
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http://dx.doi.org/10.1242/dmm.044040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710021PMC
November 2020

Injection-site Reactions to Sustained-release Meloxicam in Sprague-Dawley Rats.

J Am Assoc Lab Anim Sci 2020 11 14;59(6):726-731. Epub 2020 Sep 14.

Mouse Biology Program, School of Medicine, University of California-Davis, Davis, California; Department of Pathology and Laboratory Medicine, School of Medicine, University of California-Davis, Davis, California;, Email:

An extended-release formulation of the NSAID meloxicam (MSR) is used to provide 72 h of continuous analgesia in many species, including rodents. Although standard formulations of meloxicam are frequently used in rats with no observable injection-site reactions, the potential adverse effects from MSR have not been characterized sufficiently nor has a prospective study of these effects been performed in rats. To address this deficiency, we evaluated injection-site reactions after a single subcutaneous administration of MSR ( = 16) or sterile saline (SC, = 6) in the flank of age- and sex-matched Sprague-Dawley rats. Mass and erythema scores were measured daily for 2 wk, and injection sites were collected for histopathology after euthanasia. Rats were randomly selected for euthanasia at 7 d ( = 12) or 14 d ( = 10) after injection to capture the subacute and chronic phases of mass and erythematic lesion formation. No rats in the SC group developed lesions, whereas all 16 MSR-treated rats developed masses. The median time to first mass in the MSR treatment group was 3 d (95% CI, 2-3 d), and nearly 8 d for erythema (95% CI, 6.7-9.1 d). The trajectory of mass lesion severity showed rapid progression from score 1 at onset (day 2 or 3) to score 2 for almost all animals by day 5 or 6. Histopathology was characterized by localized inflammation with central necrosis and peripheral fibrosis, with some sections showing developing draining tracts. Given the high prevalence and severity of localized skin reactions, MSR analgesia should be considered carefully for Sprague-Dawley rats.
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http://dx.doi.org/10.30802/AALAS-JAALAS-20-000014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604686PMC
November 2020

The Dominance of Blended Emotions: A Qualitative Study of Elementary Teachers' Emotions Related to Mathematics Teaching.

Front Psychol 2020 6;11:1865. Epub 2020 Aug 6.

Department of Curriculum and Instruction, Indiana University, Bloomington, IN, United States.

Examining the nature of teachers' emotions and how they are managed and regulated in the act of teaching is crucial to assess the quality of teachers' instruction. Despite the essential role emotions play in teachers' lives and instruction, research on teachers' emotions has not paid much attention on teachers' emotions in the context of daily teaching. This paper explored elementary teachers' emotions while preparing for teaching and during teaching mathematics, reasons that underlie these emotions, and the relationship between their emotions and the quality of their mathematics instruction. Participants were seven elementary teachers working in the U.S. who participated in Holistic Individualized Coaching (HIC) professional development that consisted of five cycles of coaching over an year. For each coaching cycle, pre-coaching conversation and post-coaching conversation data were collected regarding emotions teachers felt in anticipation of teaching and during teaching retrospectively. In order to compare teachers' emotions with instructional quality, coaching sessions were video recorded and analyzed to determine the quality of instruction. Findings of this study showed that teachers reported six categories of emotions (positive, negative, neutral, blended-positive, blended-negative, and mixed), described emotions often in non-typical ways (e.g., "not nervous", "anxious but in a positive way"), and experienced mixed emotions (co-occcurence of positive and negative emotions) as the most dominant emotion. Teachers also had more positive emotions anticipating teaching than actually teaching the lesson. The reason teachers felt mixed emotions reflected the complex and context-specific nature of teaching, a phenonemenon not currently described in the teacher emotion literature. There were no clear relationships between emotional experiences and instructional quality. This study allowed participants to freely describe their authentic, complex, overlapping, and ambiguous emotions in the context of active teaching, which contributes opening up the possibilities of diversifying teacher emotion research and shows the significance and usefulness of understanding teachers' emotions related to active instruction.
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http://dx.doi.org/10.3389/fpsyg.2020.01865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438925PMC
August 2020

Generation of desminopathy in rats using CRISPR-Cas9.

J Cachexia Sarcopenia Muscle 2020 10 7;11(5):1364-1376. Epub 2020 Sep 7.

Department of Physiology and Membrane Biology, University of California, Davis, CA, USA.

Background: Desminopathy is a clinically heterogeneous muscle disease caused by over 60 different mutations in desmin. The most common mutation with a clinical phenotype in humans is an exchange of arginine to proline at position 350 of desmin leading to p.R350P. We created the first CRISPR-Cas9 engineered rat model for a muscle disease by mirroring the R350P mutation in humans.

Methods: Using CRISPR-Cas9 technology, Des c.1045-1046 (AGG > CCG) was introduced into exon 6 of the rat genome causing p.R349P. The genotype of each animal was confirmed via quantitative PCR. Six male rats with a mutation in desmin (n = 6) between the age of 120-150 days and an equal number of wild type littermates (n = 6) were used for experiments. Maximal plantar flexion force was measured in vivo and combined with the collection of muscle weights, immunoblotting, and histological analysis. In addition to the baseline phenotyping, we performed a synergist ablation study in the same animals.

Results: We found a difference in the number of central nuclei between desmin mutants (1 ± 0.4%) and wild type littermates (0.2 ± 0.1%; P < 0.05). While muscle weights did not differ, we found the levels of many structural proteins to be altered in mutant animals. Dystrophin and syntrophin were increased 54% and 45% in desmin mutants, respectively (P < 0.05). Dysferlin and Annexin A2, proteins associated with membrane repair, were increased two-fold and 32%, respectively, in mutants (P < 0.05). Synergist ablation caused similar increases in muscle weight between mutant and wild type animals, but changes in fibre diameter revealed that fibre hypertrophy in desmin mutants was hampered compared with wild type animals (P < 0.05).

Conclusions: We created a novel animal model for desminopathy that will be a useful tool in furthering our understanding of the disease. While mutant animals at an age corresponding to a preclinical age in humans show no macroscopic differences, microscopic and molecular changes are already present. Future studies should aim to further decipher those biological changes that precede the clinical progression of disease and test therapeutic approaches to delay disease progression.
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http://dx.doi.org/10.1002/jcsm.12619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567154PMC
October 2020

A quantitative survey of consumer perceptions of smart food packaging in China.

Food Sci Nutr 2020 Aug 7;8(8):3977-3988. Epub 2020 Jul 7.

College of Food Science and Nutritional Engineering China Agricultural University Beijing China.

This study quantified the acceptability of smart food packaging technologies and determined their associations with sociodemographic, attitudinal, and behavioral characteristics of consumers in China. Two quantitative surveys were conducted using an intercept method in Beijing with one for intelligent food packaging and the other for active food packaging. Chi-square tests of independence and contingency tables were used to determine the acceptability of smart food packaging and significant associations with multiple variables. Smart packaging was accepted by 56% of participants in both surveys. Marital status and employment status were associated with the acceptance of active packaging, while consumer interactions with current food packaging were associated with the acceptance of intelligent packaging. Acceptance of both active and intelligent packaging was associated with trust in multiple institutions. This study is the first to provide broad information about Chinese consumers' acceptance of smart packaging technologies for food products. Findings from this research can contribute to further detailed consumer studies in product-specific packaging designs.
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http://dx.doi.org/10.1002/fsn3.1563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455960PMC
August 2020

Sustainable Personal Protective Clothing for Healthcare Applications: A Review.

ACS Nano 2020 10 24;14(10):12313-12340. Epub 2020 Sep 24.

Department of Materials Science and Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117575.

Personal protective equipment (PPE) is critical to protect healthcare workers (HCWs) from highly infectious diseases such as COVID-19. However, hospitals have been at risk of running out of the safe and effective PPE including personal protective clothing needed to treat patients with COVID-19, due to unprecedented global demand. In addition, there are only limited manufacturing facilities of such clothing available worldwide, due to a lack of available knowledge about relevant technologies, ineffective supply chains, and stringent regulatory requirements. Therefore, there remains a clear unmet need for coordinating the actions and efforts from scientists, engineers, manufacturers, suppliers, and regulatory bodies to develop and produce safe and effective protective clothing using the technologies that are locally available around the world. In this review, we discuss currently used PPE, their quality, and the associated regulatory standards. We survey the current state-of-the-art antimicrobial functional finishes on fabrics to protect the wearer against viruses and bacteria and provide an overview of protective medical fabric manufacturing techniques, their supply chains, and the environmental impacts of current single-use synthetic fiber-based protective clothing. Finally, we discuss future research directions, which include increasing efficiency, safety, and availability of personal protective clothing worldwide without conferring environmental problems.
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http://dx.doi.org/10.1021/acsnano.0c05537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518242PMC
October 2020

Woeseiales transcriptional response to shallow burial in Arctic fjord surface sediment.

PLoS One 2020 27;15(8):e0234839. Epub 2020 Aug 27.

Department of Microbiology, University of Tennessee, Knoxville, Tennessee, United States of America.

Distinct lineages of Gammaproteobacteria clade Woeseiales are globally distributed in marine sediments, based on metagenomic and 16S rRNA gene analysis. Yet little is known about why they are dominant or their ecological role in Arctic fjord sediments, where glacial retreat is rapidly imposing change. This study combined 16S rRNA gene analysis, metagenome-assembled genomes (MAGs), and genome-resolved metatranscriptomics uncovered the in situ abundance and transcriptional activity of Woeseiales with burial in four shallow sediment sites of Kongsfjorden and Van Keulenfjorden of Svalbard (79°N). We present five novel Woeseiales MAGs and show transcriptional evidence for metabolic plasticity during burial, including sulfur oxidation with reverse dissimilatory sulfite reductase (dsrAB) down to 4 cm depth and nitrite reduction down to 6 cm depth. A single stress protein, spore protein SP21 (hspA), had a tenfold higher mRNA abundance than any other transcript, and was a hundredfold higher on average than other transcripts. At three out of the four sites, SP21 transcript abundance increased with depth, while total mRNA abundance and richness decreased, indicating a shift in investment from metabolism and other cellular processes to build-up of spore protein SP21. The SP21 gene in MAGs was often flanked by genes involved in membrane-associated stress response. The ability of Woeseiales to shift from sulfur oxidation to nitrite reduction with burial into marine sediments with decreasing access to overlying oxic bottom waters, as well as enter into a dormant state dominated by SP21, may account for its ubiquity and high abundance in marine sediments worldwide, including those of the rapidly shifting Arctic.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234839PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451513PMC
October 2020

High fat diet consumption restricted to adolescence has minimal effects on adult executive function that vary by sex.

Nutr Neurosci 2020 Aug 25:1-11. Epub 2020 Aug 25.

Pharmacology and Systems Physiology, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.

Early life environment can have a lasting effect on brain development and behavior. Diet is a potent environmental factor that can positively or negatively affect neurodevelopment, and unfortunately, the likelihood of a poor diet is high during adolescence. Adverse effects of adolescent high fat diet have been observed on reward-related behaviors, reversal learning, and hippocampal-dependent learning tasks in rodents when tested in adulthood. The prefrontal cortex (PFC) continues to develop throughout adolescence and is thus vulnerable to environmental insults such as poor diet. Therefore, we sought to examine the effects of a high fat diet (HFD) consumed only during adolescence on later life adult PFC-dependent executive function. Male and female mice were fed a HFD (60% energy from fat) during either early or late adolescence then switched to standard chow and tested in a battery of touchscreen-based operant tests of executive function in adulthood. Contrary to our prediction of an adverse effect of HFD, there was no effect of adolescent HFD in males, and females showed faster learning and decreased inattention in adulthood. We conclude that the effects of adolescent-limited HFD on adult executive function are mild, positive, and vary by sex.
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http://dx.doi.org/10.1080/1028415X.2020.1809879DOI Listing
August 2020

Negative reinforcement rate and persistent avoidance following response-prevention extinction.

Behav Res Ther 2020 Aug 12;133:103711. Epub 2020 Aug 12.

Experimental Psychopathology Lab, Department of Psychology, Swansea University, Singleton Campus, Swansea, SA2 8PP, United Kingdom; Department of Psychology, Reykjavík University, Menntavegur 1, KU Leuven, 101, Reykjavík, Iceland. Electronic address:

Persistent avoidance may be influenced by prior negative reinforcement rate (i.e., how effective the response is at controlling threat). In clinical settings, the effectiveness of extinction-based methods for treating anxiety-related avoidance may be impacted by prior reinforcement rate. Here, we conducted a laboratory-based treatment study to investigate the persistence of avoidance following response-prevention extinction (RPE) when prior avoidance had been differentially effective at cancelling shock. Participants in three negative reinforcement rate groups (100%, 50%, and 0%) completed a validated avoidance conditioning paradigm involving Pavlovian fear extinction, RPE, and re-extinction phases. It was hypothesised that partially reinforced avoidance would lead to diminished resistance to fear extinction following response prevention, compared to continuously- or never-reinforced avoidance. Persistent avoidance was related to prior negative reinforcement rate, with higher rates more resistant to extinction. These findings illustrate the role of reinforcement rate in the persistence of avoidance and may aid understanding of treatment relapse.
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http://dx.doi.org/10.1016/j.brat.2020.103711DOI Listing
August 2020

Dynamic Properties of Heart Fragments from Different Regions and Their Synchronization.

Bioengineering (Basel) 2020 Jul 29;7(3). Epub 2020 Jul 29.

Department of Physics and Mathematics, College of Science and Engineering, Aoyama Gakuin University, Kanagawa 252-5258, Japan.

The dynamic properties of the heart differ based on the regions that effectively circulate blood throughout the body with each heartbeat. These properties, including the inter-beat interval (IBI) of autonomous beat activity, are retained even in in vitro tissue fragments. However, details of beat dynamics have not been well analyzed, particularly at the sub-mm scale, although such dynamics of size are important for regenerative medicine and computational studies of the heart. We analyzed the beat dynamics in sub-mm tissue fragments from atria and ventricles of hearts obtained from chick embryos over a period of 40 h. The IBI and contraction speed differed by region and atrial fragments retained their values for a longer time. The major finding of this study is synchronization of these fragment pairs physically attached to each other. The probability of achieving this and the time required differ for regional pairs: atrium-atrium, ventricle-ventricle, or atrium-ventricle. Furthermore, the time required to achieve 1:1 synchronization does not depend on the proximity of initial IBI of paired fragments. Various interesting phenomena, such as 1:n synchronization and a reentrant-like beat sequence, are revealed during synchronization. Finally, our observation of fragment dynamics indicates that mechanical motion itself contributes to the synchronization of atria.
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http://dx.doi.org/10.3390/bioengineering7030081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552607PMC
July 2020

Dynamic Properties of Heart Fragments from Different Regions and Their Synchronization.

Bioengineering (Basel) 2020 Jul 29;7(3). Epub 2020 Jul 29.

Department of Physics and Mathematics, College of Science and Engineering, Aoyama Gakuin University, Kanagawa 252-5258, Japan.

The dynamic properties of the heart differ based on the regions that effectively circulate blood throughout the body with each heartbeat. These properties, including the inter-beat interval (IBI) of autonomous beat activity, are retained even in in vitro tissue fragments. However, details of beat dynamics have not been well analyzed, particularly at the sub-mm scale, although such dynamics of size are important for regenerative medicine and computational studies of the heart. We analyzed the beat dynamics in sub-mm tissue fragments from atria and ventricles of hearts obtained from chick embryos over a period of 40 h. The IBI and contraction speed differed by region and atrial fragments retained their values for a longer time. The major finding of this study is synchronization of these fragment pairs physically attached to each other. The probability of achieving this and the time required differ for regional pairs: atrium-atrium, ventricle-ventricle, or atrium-ventricle. Furthermore, the time required to achieve 1:1 synchronization does not depend on the proximity of initial IBI of paired fragments. Various interesting phenomena, such as 1:n synchronization and a reentrant-like beat sequence, are revealed during synchronization. Finally, our observation of fragment dynamics indicates that mechanical motion itself contributes to the synchronization of atria.
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http://dx.doi.org/10.3390/bioengineering7030081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552607PMC
July 2020

Evidence for a Growth Zone for Deep-Subsurface Microbial Clades in Near-Surface Anoxic Sediments.

Appl Environ Microbiol 2020 09 17;86(19). Epub 2020 Sep 17.

University of Tennessee, Knoxville, Tennessee, USA.

Global marine sediments harbor a large and highly diverse microbial biosphere, but the mechanism by which this biosphere is established during sediment burial is largely unknown. During burial in marine sediments, concentrations of easily metabolized organic compounds and total microbial cell abundance decrease. However, it is unknown whether some microbial clades increase with depth. We show total population increases in 38 microbial families over 3 cm of sediment depth in the upper 7.5 cm of White Oak River (WOR) estuary sediments. Clades that increased with depth were more often associated with one or more of the following: anaerobes, uncultured, or common in deep marine sediments relative to those that decreased. Maximum doubling times ( steady-state growth rates could be faster to balance cell decay) were estimated as 2 to 25 years by combining sedimentation rate with either quantitative PCR (qPCR) or the product of the fraction read abundance of 16S rRNA genes and total cell counts (FRAxC). Doubling times were within an order of magnitude of each other in two adjacent cores, as well as in two laboratory enrichments of Cape Lookout Bight (CLB), NC, sediments (average difference of 28% ± 19%). qPCR and FRAxC in sediment cores and laboratory enrichments produced similar doubling times for key deep subsurface uncultured clades (8.7 ± 1.9 years) and /MBG-D (4.1 ± 0.7 years). We conclude that common deep subsurface microbial clades experience a narrow zone of growth in shallow sediments, offering an opportunity for selection of long-term subsistence traits after resuspension events. Many studies show that the uncultured microbes that dominate global marine sediments do not actually increase in population size as they are buried in marine sediments; rather, they exist in a sort of prolonged torpor for thousands of years. This is because, although studies have shown biomass turnover in these clades, no evidence has ever been found that deeper sediments have larger populations for specific clades than shallower layers. We discovered that they actually do increase population sizes during burial, but only in the upper few centimeters. This suggests that marine sediments may be a vast repository of mostly nongrowing microbes with a thin and relatively rapid area of cell abundance increase in the upper 10 cm, offering a chance for subsurface organisms to undergo natural selection.
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http://dx.doi.org/10.1128/AEM.00877-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499048PMC
September 2020

Coupling of energy intake and energy expenditure across a temperature spectrum: impact of diet-induced obesity in mice.

Am J Physiol Endocrinol Metab 2020 09 21;319(3):E472-E484. Epub 2020 Jul 21.

Arkansas Children's Nutrition Center, Little Rock, Arkansas.

Obesity and its metabolic sequelae are implicated in dysfunction of the somatosensory, sympathetic, and hypothalamic systems. Because these systems contribute to integrative regulation of energy expenditure (EE) and energy intake (EI) in response to ambient temperature (T) changes, we hypothesized that diet-induced obesity (DIO) disrupts T-associated EE-EI coupling. C57BL/6N male mice were fed a high-fat diet (HFD; 45% kcal) or low-fat diet (LFD; 10% kcal) for ∼9.5 wk; HFD mice were then split into body weight (BWT) quartiles ( = 8 each) to study DIO-low gainers (Q1) versus -high gainers (Q4). EI and indirect calorimetry (IC) were measured over 3 days each at 10°C, 20°C, and 30°C. Responses did not differ between LFD, Q1, and Q4; EI and BWT-adjusted EE increased rapidly when transitioning toward 20°C and 10°C. In all groups, EI at 30°C was not reduced despite lower EE, resulting in positive energy balance and respiratory exchange ratios consistent with increased de novo lipogenesis, energy storage, and relative hyperphagia. We conclude that ) systems controlling T-dependent acute EI/EE coupling remained intact in obese mice and ) rapid coupling of EI/EE at cooler temperatures is an important adaptation to maintain energy stores and defend body temperature, but less critical at thermoneutrality. A post hoc analysis using digestible EI plus IC-calculated EE suggests that standard IC assumptions for EE calculation require further validation in the setting of DIO. The experimental paradigm provides a platform to query the hypothalamic, somatosensory, and sympathetic mechanisms that drive T-associated EI/EE coupling.
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http://dx.doi.org/10.1152/ajpendo.00041.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509245PMC
September 2020

Synthesis and Properties of Perylene-Bridge-Anchor Chromophoric Compounds.

J Phys Chem A 2020 Aug 27;124(31):6330-6343. Epub 2020 Jul 27.

Department of Chemistry, Rutgers University, Newark, New Jersey 07102, United States.

The quest to control chromophore/semiconductor properties to enable new technologies in energy and information science requires detailed understanding of charge carrier dynamics at the atomistic level, which can often be attained through the use of model systems. Perylene-bridge-anchor compounds are successful models for studying fundamental charge transfer processes on TiO, which remains among the most commonly investigated and technologically important interfaces, mostly because of perylene's advantageous electronic and optical properties. Nonetheless, the ability to fully exploit synthetically the substitution pattern of perylene with linker (= bridge-anchor) units remains little explored. Here we developed 2,5-di--butylperylene (DtBuPe)-bridge-anchor compounds with -Bu group substituents to prevent π-stacking and one or two linker units in both the and positions, by employing a combination of Friedel-Crafts alkylations, bromination, iridium-catalyzed borylation, and palladium-catalyzed cross-coupling reactions. Photophysical characterization and computational analysis by density functional theory (DFT) and time-dependent DFT (TD-DFT) were carried out on four DtBuPe acrylic acid derivatives with a single or a double linker in (), (), , (), and , (). The energies of the unoccupied orbitals {LUMO, LUMO + 1, LUMO + 2} are strongly affected by the presence of a π-conjugated linker, resulting in a stabilization of these states and a red shift of their absorption and emission spectra, as well as the loss of vibronic structure in the spectrum of the , compound, consistent with the strong bonding character of this substitution pattern.
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http://dx.doi.org/10.1021/acs.jpca.0c04609DOI Listing
August 2020

Driving in Parkinson's disease: a retrospective study of driving and mobility assessments.

Age Ageing 2020 10;49(6):1097-1101

Population Health Sciences, University of Bristol, Bristol, UK.

Background: To guide decision-making about driving ability, some patients with Parkinson's disease (PD) undergo specialist driving assessment. However, decisions about driving safety in most patients need to be made without this definitive test. There is no consensus on what predicts unsafe driving in PD nor a validated prediction tool to guide clinician decision-making and the need to refer for further assessment.

Objectives: To describe the characteristics of patients with PD assessed at a Driving Mobility Centre and investigate factors that predict driving assessment outcome.

Methods: Retrospective cohort study of patients with PD assessed between 2012 and 2016. Descriptive analyses and logistic models to determine factors predicting a negative outcome.

Results: There were 86 assessments of patients with PD. The mean age was 70 years (±9.2), 86% were male, median disease duration 7 years (interquartile range 5-12.5 years) and 59% were referred by the Driver and Vehicle Licensing Agency. In total, 62% had a negative 'not drive' outcome. The Rookwood Driving Battery (RDB), depth of vision deficit, usual driving frequency, age, duration license held and response time were all predictors in univariable analysis. The RDB was the best predictor of assessment failure, conditional on other variables in a backward stepwise model (odds ratio 1.29; 95% confidence interval 1.05, 1.60; P = 0.015).

Conclusions: This is the first study to describe patients with PD undergoing driving assessments in the UK. In this population, RDB performance was the best predictor of outcome. Future prospective studies are required to better determine predictors of driving ability to guide development of prediction tools for implementation into clinical practice.
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http://dx.doi.org/10.1093/ageing/afaa098DOI Listing
October 2020

Roadmap for naming uncultivated Archaea and Bacteria.

Nat Microbiol 2020 08 8;5(8):987-994. Epub 2020 Jun 8.

National Museum of Natural Sciences, CSIC, Madrid, Spain.

The assembly of single-amplified genomes (SAGs) and metagenome-assembled genomes (MAGs) has led to a surge in genome-based discoveries of members affiliated with Archaea and Bacteria, bringing with it a need to develop guidelines for nomenclature of uncultivated microorganisms. The International Code of Nomenclature of Prokaryotes (ICNP) only recognizes cultures as 'type material', thereby preventing the naming of uncultivated organisms. In this Consensus Statement, we propose two potential paths to solve this nomenclatural conundrum. One option is the adoption of previously proposed modifications to the ICNP to recognize DNA sequences as acceptable type material; the other option creates a nomenclatural code for uncultivated Archaea and Bacteria that could eventually be merged with the ICNP in the future. Regardless of the path taken, we believe that action is needed now within the scientific community to develop consistent rules for nomenclature of uncultivated taxa in order to provide clarity and stability, and to effectively communicate microbial diversity.
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http://dx.doi.org/10.1038/s41564-020-0733-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381421PMC
August 2020

Healthier school food and physical activity environments are associated with lower student body mass index.

Prev Med Rep 2020 Sep 8;19:101115. Epub 2020 May 8.

College of Health Solutions. Arizona State University. 500 N. 3rd Street, Phoenix, AZ 85004, United States.

School food and physical activity (PA) environments can influence children's dietary and physical activity behaviors. However, evidence on whether school environment is associated with students' weight status is less definitive. In this study, we examined the association between students' body mass index (BMI) and measures of school food and PA environments. We calculated BMI from nurse-measured data collected on 19,188 6-19-year-old students from 90 public schools in four low-income cities in New Jersey in 2015-2016. Based on a questionnaire administered to school nurses, we constructed 6 food and 3 PA indices capturing the healthfulness of key dimensions in the school food and PA environment domains. Multilevel linear models, stratified by school level (elementary and secondary), examined the association between BMI z-scores and indices of the school environment. The food and PA domains were modeled separately and then combined. Joint significance of indices within each domain was tested. Analyses were conducted in 2019-2020. In the combined model for elementary schools, indices in both the food and PA domains were jointly significant (p = 0.005 and p < 0.001, respectively). With regard to specific indices in the model, students' BMI z-score was 0.03 units lower for each additional outdoor PA facility (95% CI [-0.06, -0.00]; p = 0.036). Similarly, for secondary schools, both the food and PA domains were jointly significant (p = 0.004 and p = 0.020, respectively). Each additional unhealthy item in vending machines was associated with a 0.12 unit increase in BMI z-score (95% CI [+0.00, 0.23]; p = 0.042). Overall, healthier food and PA environments were associated with lower student BMI.
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http://dx.doi.org/10.1016/j.pmedr.2020.101115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264762PMC
September 2020

Treading water: mixed effects of high fat diet on mouse behavior in the forced swim test.

Physiol Behav 2020 09 23;223:112965. Epub 2020 May 23.

University of Cincinnati, College of Medicine, Department of Pharmacology and Systems Physiology. Electronic address:

Diet is an environmental factor with significant potential to affect the brain and behavior in both positive and negative ways. Work in animals is necessary to understand this relationship and how it may apply to mental health in humans. One area which has been investigated extensively is whether diet, specifically a high fat diet (HFD), can alter behavior in tasks, such as the forced swim test (FST) that assess stress coping. Therefore, we sought to analyze the literature regarding the effect of HFD on performance in the FST to determine whether there was a consistent effect of HFD on stress coping behavior. We conducted a Google Scholar search of English-language articles with the following terms: high fat diet, obesity, forced swim test, depression like behavior, mouse. Thirty studies from twenty-five publications are included in this survey. Fifteen studies were found where HFD had no effect on FST, 4 where HFD decreased immobility, and 11 where HFD increased immobility. Experimental details in these studies varied widely, including differences in the diet, mice, and experimental design. Additionally, we analyzed thirteen studies that performed the tail-suspension test (TST) after HFD, with six studies finding no change due to HFD and 7 reporting that HFD increased immobility. Further, 6 of these studies used both FST and TST with largely similar results in the two tasks, indicating concordance between the two tests of stress-coping behavior. We conclude that due to widely varying experimental details across studies no consistent effect of high fat diet on stress coping behavior can be determined at this point.
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http://dx.doi.org/10.1016/j.physbeh.2020.112965DOI Listing
September 2020

Author Correction: Diversity, ecology and evolution of Archaea.

Nat Microbiol 2020 Jul;5(7):976

Microbiology Department, University of Tennessee, Knoxville, TN, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41564-020-0741-xDOI Listing
July 2020

COVID-19 in older people: a rapid clinical review.

Age Ageing 2020 07;49(4):501-515

Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Introduction: the COVID-19 pandemic poses a high risk to older people. The aim of this article is to provide a rapid overview of the COVID-19 literature, with a specific focus on older adults. We frame our findings within an overview of the disease and have also evaluated the inclusion of older people within forthcoming clinical trials.

Methods: we searched PubMed and bioRxiv/medRxiv to identify English language papers describing the testing, treatment and prognosis of COVID-19. PubMed and bioRxiv/medRxiv searches took place on 20 and 24 March 2020, respectively.

Results: screening of over 1,100 peer-reviewed and pre-print papers yielded n = 22 on COVID-19 testing, n = 15 on treatment and n = 13 on prognosis. Viral polymerase chain reaction (PCR) and serology are the mainstays of testing, but a positive diagnosis may be increasingly supported by radiological findings. The current evidence for the effectiveness of antiviral, corticosteroid and immunotherapies is inconclusive, although trial data are largely based on younger people. In addition to age, male gender and comorbidities, specific laboratory and radiology findings are important prognostic factors. Evidence suggests that social distancing policies could have important negative consequences, particularly if in place for an extended period.

Conclusion: given the established association between increasing age and poor prognosis in COVID-19, we anticipate that this rapid review of the current and emergent evidence might form a basis on which future work can be established. Exclusion of older people, particularly those with comorbidities, from clinical trials is well recognised and is potentially being perpetuated in the field of current COVID-19 research.
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http://dx.doi.org/10.1093/ageing/afaa093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239238PMC
July 2020

Diversity, ecology and evolution of Archaea.

Nat Microbiol 2020 07 4;5(7):887-900. Epub 2020 May 4.

Microbiology Department, University of Tennessee, Knoxville, TN, USA.

Compared to bacteria, our knowledge of archaeal biology is limited. Historically, microbiologists have mostly relied on culturing and single-gene diversity surveys to understand Archaea in nature. However, only six of the 27 currently proposed archaeal phyla have cultured representatives. Advances in genomic sequencing and computational approaches are revolutionizing our understanding of Archaea. The recovery of genomes belonging to uncultured groups from the environment has resulted in the description of several new phyla, many of which are globally distributed and are among the predominant organisms on the planet. In this Review, we discuss how these genomes, together with long-term enrichment studies and elegant in situ measurements, are providing insights into the metabolic capabilities of the Archaea. We also debate how such studies reveal how important Archaea are in mediating an array of ecological processes, including global carbon and nutrient cycles, and how this increase in archaeal diversity has expanded our view of the tree of life and early archaeal evolution, and has provided new insights into the origin of eukaryotes.
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http://dx.doi.org/10.1038/s41564-020-0715-zDOI Listing
July 2020

Specificity of bispecific T cell receptors and antibodies targeting peptide-HLA.

J Clin Invest 2020 05;130(5):2673-2688

Immunocore Ltd., Milton Park, Abingdon, United Kingdom.

Tumor-associated peptide-human leukocyte antigen complexes (pHLAs) represent the largest pool of cell surface-expressed cancer-specific epitopes, making them attractive targets for cancer therapies. Soluble bispecific molecules that incorporate an anti-CD3 effector function are being developed to redirect T cells against these targets using 2 different approaches. The first achieves pHLA recognition via affinity-enhanced versions of natural TCRs (e.g., immune-mobilizing monoclonal T cell receptors against cancer [ImmTAC] molecules), whereas the second harnesses an antibody-based format (TCR-mimic antibodies). For both classes of reagent, target specificity is vital, considering the vast universe of potential pHLA molecules that can be presented on healthy cells. Here, we made use of structural, biochemical, and computational approaches to investigate the molecular rules underpinning the reactivity patterns of pHLA-targeting bispecifics. We demonstrate that affinity-enhanced TCRs engage pHLA using a comparatively broad and balanced energetic footprint, with interactions distributed over several HLA and peptide side chains. As ImmTAC molecules, these TCRs also retained a greater degree of pHLA selectivity, with less off-target activity in cellular assays. Conversely, TCR-mimic antibodies tended to exhibit binding modes focused more toward hot spots on the HLA surface and exhibited a greater degree of crossreactivity. Our findings extend our understanding of the basic principles that underpin pHLA selectivity and exemplify a number of molecular approaches that can be used to probe the specificity of pHLA-targeting molecules, aiding the development of future reagents.
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http://dx.doi.org/10.1172/JCI130562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190993PMC
May 2020

Area deprivation, urbanicity, severe mental illness and social drift - A population-based linkage study using routinely collected primary and secondary care data.

Schizophr Res 2020 06 2;220:130-140. Epub 2020 Apr 2.

HDRUK, Swansea University Medical School, Singleton Park, Swansea SA2 8PP, UK; National Centre for Mental Health, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, UK. Electronic address:

We investigated whether associations between area deprivation, urbanicity and elevated risk of severe mental illnesses (SMIs, including schizophrenia and bipolar disorder) is accounted for by social drift or social causation. We extracted primary and secondary care electronic health records from 2004 to 2015 from a population of 3.9 million. We identified prevalent and incident individuals with SMIs and their level of deprivation and urbanicity using the Welsh Index of Multiple Deprivation (WIMD) and urban/rural indicator. The presence of social drift was determined by whether odds ratios (ORs) from logistic regression is greater than the incidence rate ratios (IRRs) from Poisson regression. Additionally, we performed longitudinal analysis to measure the proportion of change in deprivation level and rural/urban residence 10 years after an incident diagnosis of SMI and compared it to the general population using standardised rate ratios (SRRs). Prevalence and incidence of SMIs were significantly associated with deprivation and urbanicity (all ORs and IRRs significantly >1). ORs and IRRs were similar across all conditions and cohorts (ranging from 1.1 to 1.4). Results from the longitudinal analysis showed individuals with SMIs are more likely to move compared to the general population. However, they did not preferentially move to more deprived or urban areas. There was little evidence of downward social drift over a 10-year period. These findings have implications for the allocation of resources, service configuration and access to services in deprived communities, as well as, for broader public health interventions addressing poverty, and social and environmental contexts.
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http://dx.doi.org/10.1016/j.schres.2020.03.044DOI Listing
June 2020

Chromium propionate increases insulin sensitivity in horses following oral and intravenous carbohydrate administration.

J Anim Sci 2020 Apr;98(4)

Kemin AgriFoods North America, Inc., Des Moines, IA.

Forty-eight Quarter Horse geldings (3 to 8 yr of age) were used to determine the effects of dietary chromium (Cr), in the form of Cr propionate (Cr Prop) on insulin sensitivity. Horses were blocked by age, body condition score, and glucose response to concentrate feeding on day 0 and randomly assigned to treatments. Treatments consisted of 0, 2, 4, or 8 mg Cr/d from Cr Prop. Horses were fed daily a concentrate mix at a rate of 0.2 kg/100 kg body weight (BW) and grass hay at 1.75 to 2.0 kg/100 kg BW. All horses were fed the control diet for 7 d prior to the initiation of the study. After an overnight fast, blood samples from the jugular vein were obtained at 0, 2, and 4 h after concentrate feeding on days 0 and 28 for the determination of glucose, nonesterified fatty acids, and insulin. A glucose tolerance test (GTT) was conducted on day 42. Glucose was infused via jugular vein catheters, and blood samples were collected at various times relative to dosing for glucose and insulin determination. Plasma glucose on day 28 was affected (P < 0.05) by treatment, time, and treatment × time. Horses fed 4 mg Cr/d had lesser (P < 0.05) plasma glucose concentrations than those in the other treatments at 0 h. At 2 h post-feeding glucose concentrations were greater (P < 0.05) in horses fed 0 or 8 mg Cr/d than in those given 4 mg Cr. Horses fed 2 mg Cr/d had lesser (P < 0.05) plasma glucose at 4 h post feeding compared with those fed 0 or 8 mg Cr. Plasma glucose did not differ among horses receiving 2 or 4 mg Cr/d at 2 or 4 h. Serum insulin was affected (P < 0.05) by treatment, time, and treatment × time. Insulin concentrations were greater (P < 0.05) in horses fed 0 or 2 mg Cr/d than in those given 4 or 8 mg Cr at 0 h. At 4 h post-feeding insulin concentrations were greater (P < 0.05) in horses given 0 or 8 mg Cr than in those fed 2 or 4 mg Cr/d. Plasma glucose was affected (P < 0.05) by treatment and time, but not by treatment × time following the GTT. Mean plasma glucose (across sampling times) concentrations were greater (P < 0.05) in controls than in horses fed 2 or 4 mg Cr/d. Glucose concentrations following the GTT did not differ among controls and horses given 8 mg Cr/d. Following glucose infusion, serum insulin concentrations were greater (P < 0.05) in horses fed 2 or 4 mg Cr and tended to be greater in those fed 8 mg Cr/d compared with controls. The results of this study indicate that 2 or 4 mg Cr/d from Cr Prop increased insulin sensitivity in adult horses following oral carbohydrate consumption.
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http://dx.doi.org/10.1093/jas/skaa095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323256PMC
April 2020

Chromium propionate increases insulin sensitivity in horses following oral and intravenous carbohydrate administration.

J Anim Sci 2020 Apr;98(4)

Kemin AgriFoods North America, Inc., Des Moines, IA.

Forty-eight Quarter Horse geldings (3 to 8 yr of age) were used to determine the effects of dietary chromium (Cr), in the form of Cr propionate (Cr Prop) on insulin sensitivity. Horses were blocked by age, body condition score, and glucose response to concentrate feeding on day 0 and randomly assigned to treatments. Treatments consisted of 0, 2, 4, or 8 mg Cr/d from Cr Prop. Horses were fed daily a concentrate mix at a rate of 0.2 kg/100 kg body weight (BW) and grass hay at 1.75 to 2.0 kg/100 kg BW. All horses were fed the control diet for 7 d prior to the initiation of the study. After an overnight fast, blood samples from the jugular vein were obtained at 0, 2, and 4 h after concentrate feeding on days 0 and 28 for the determination of glucose, nonesterified fatty acids, and insulin. A glucose tolerance test (GTT) was conducted on day 42. Glucose was infused via jugular vein catheters, and blood samples were collected at various times relative to dosing for glucose and insulin determination. Plasma glucose on day 28 was affected (P < 0.05) by treatment, time, and treatment × time. Horses fed 4 mg Cr/d had lesser (P < 0.05) plasma glucose concentrations than those in the other treatments at 0 h. At 2 h post-feeding glucose concentrations were greater (P < 0.05) in horses fed 0 or 8 mg Cr/d than in those given 4 mg Cr. Horses fed 2 mg Cr/d had lesser (P < 0.05) plasma glucose at 4 h post feeding compared with those fed 0 or 8 mg Cr. Plasma glucose did not differ among horses receiving 2 or 4 mg Cr/d at 2 or 4 h. Serum insulin was affected (P < 0.05) by treatment, time, and treatment × time. Insulin concentrations were greater (P < 0.05) in horses fed 0 or 2 mg Cr/d than in those given 4 or 8 mg Cr at 0 h. At 4 h post-feeding insulin concentrations were greater (P < 0.05) in horses given 0 or 8 mg Cr than in those fed 2 or 4 mg Cr/d. Plasma glucose was affected (P < 0.05) by treatment and time, but not by treatment × time following the GTT. Mean plasma glucose (across sampling times) concentrations were greater (P < 0.05) in controls than in horses fed 2 or 4 mg Cr/d. Glucose concentrations following the GTT did not differ among controls and horses given 8 mg Cr/d. Following glucose infusion, serum insulin concentrations were greater (P < 0.05) in horses fed 2 or 4 mg Cr and tended to be greater in those fed 8 mg Cr/d compared with controls. The results of this study indicate that 2 or 4 mg Cr/d from Cr Prop increased insulin sensitivity in adult horses following oral carbohydrate consumption.
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http://dx.doi.org/10.1093/jas/skaa095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323256PMC
April 2020

DNA fragmentation index (DFI) as a measure of sperm quality and fertility in mice.

Sci Rep 2020 03 2;10(1):3833. Epub 2020 Mar 2.

Mouse Biology Program, University of California, Davis, CA, 95618, USA.

Although thousands of genetically modified mouse strains have been cryopreserved by sperm freezing, the likelihood of cryorecovery success cannot be accurately predicted using conventional sperm parameters. The objective of the present study was to assess the extent to which measurement of a sperm DNA fragmentation index (DFI) can predict sperm quality and fertility after cryopreservation. Using a modified TUNEL assay, we measured and correlated the DFI of frozen-thawed sperm from 83 unique mutant mouse strains with sperm count, motility and morphology. We observed a linear inverse correlation between sperm DFI and sperm morphology and motility. Further, sperm DFI was significantly higher from males with low sperm counts compared to males with normal sperm counts (P < 0.0001). Additionally, we found that viable embryos derived using sperm from males with high DFI (62.7 ± 7.2% for IVF and 73.3 ± 8.1% for ICSI) failed to litter after embryo transfer compared to embryos from males with low DFI (20.4 ± 7.9% for IVF and 28.1 ± 10.7 for ICSI). This study reveals that measurement of DFI provides a simple, informative and reliable measure of sperm quality and can accurately predict male mouse fertility.
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http://dx.doi.org/10.1038/s41598-020-60876-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052244PMC
March 2020

DNA fragmentation index (DFI) as a measure of sperm quality and fertility in mice.

Sci Rep 2020 03 2;10(1):3833. Epub 2020 Mar 2.

Mouse Biology Program, University of California, Davis, CA, 95618, USA.

Although thousands of genetically modified mouse strains have been cryopreserved by sperm freezing, the likelihood of cryorecovery success cannot be accurately predicted using conventional sperm parameters. The objective of the present study was to assess the extent to which measurement of a sperm DNA fragmentation index (DFI) can predict sperm quality and fertility after cryopreservation. Using a modified TUNEL assay, we measured and correlated the DFI of frozen-thawed sperm from 83 unique mutant mouse strains with sperm count, motility and morphology. We observed a linear inverse correlation between sperm DFI and sperm morphology and motility. Further, sperm DFI was significantly higher from males with low sperm counts compared to males with normal sperm counts (P < 0.0001). Additionally, we found that viable embryos derived using sperm from males with high DFI (62.7 ± 7.2% for IVF and 73.3 ± 8.1% for ICSI) failed to litter after embryo transfer compared to embryos from males with low DFI (20.4 ± 7.9% for IVF and 28.1 ± 10.7 for ICSI). This study reveals that measurement of DFI provides a simple, informative and reliable measure of sperm quality and can accurately predict male mouse fertility.
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http://dx.doi.org/10.1038/s41598-020-60876-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052244PMC
March 2020