Publications by authors named "James A Martin"

115 Publications

De novo assembly and delivery to mouse cells of a 101 kb functional human gene.

Genetics 2021 May;218(1)

Institute for Systems Genetics, NYU Langone Health, New York, NY 10016, USA.

Design and large-scale synthesis of DNA has been applied to the functional study of viral and microbial genomes. New and expanded technology development is required to unlock the transformative potential of such bottom-up approaches to the study of larger mammalian genomes. Two major challenges include assembling and delivering long DNA sequences. Here, we describe a workflow for de novo DNA assembly and delivery that enables functional evaluation of mammalian genes on the length scale of 100 kilobase pairs (kb). The DNA assembly step is supported by an integrated robotic workcell. We demonstrate assembly of the 101 kb human HPRT1 gene in yeast from 3 kb building blocks, precision delivery of the resulting construct to mouse embryonic stem cells, and subsequent expression of the human protein from its full-length human gene in mouse cells. This workflow provides a framework for mammalian genome writing. We envision utility in producing designer variants of human genes linked to disease and their delivery and functional analysis in cell culture or animal models.
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http://dx.doi.org/10.1093/genetics/iyab038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128383PMC
May 2021

Targeting oxidative stress with amobarbital to prevent intervertebral disc degeneration: Part I. in vitro and ex vivo studies.

Spine J 2021 Jun 19;21(6):1021-1030. Epub 2021 Feb 19.

Roy J. Carver Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA.

Background: Mounting evidence that oxidative stress contributes to the pathogenesis of intervertebral disc (IVD) degeneration (IDD) suggests that therapies targeting oxidative stress may slow or prevent disease progression.

Purpose: The objective of this study was to investigate the inhibitory effects of amobarbital (Amo) on the mitochondria of nucleus pulposus (NP) cells under tert-butyl hydrogen peroxide (tBHP)-induced oxidative stress or in NP tissues under oxidative stress from tissue injury as a means of identifying therapeutic targets for IDD.

Study Design/setting: We tested the effects inhibiting mitochondria, a major source of oxidants, with Amo in NP cells subjected to two different forms of insult: exposure to tBHP, and physical injury induced by disc transection. N-acetylcysteine (NAC), an antioxidant known to protect NP cells, was compared to the complex I inhibitor, Amo.

Methods: NP cells were pre-treated for 2 hours with Amo, NAC, or both, and then exposed to tBHP for 1 hour. Apoptosis, necrosis, and reactive oxygen species (ROS) production were assessed using confocal microscopy and fluorescent probes (Annexin V, propidium iodide, and MitoSox Red, respectively). The activation of mitogen-activated protein kinases (MAPKs) involved in oxidative stress responses were interrogated by confocal imaging of immunofluorescence stains using phospho-specific antibodies to extracellular signal-regulated kinase (ERK), c-JUN N-terminal kinase (JNK), and p38. Mitochondrial function was assessed by imaging JC-1 staining, a probe for membrane potential.

Results: Amo was modestly more protective than NAC by some measures, while both agents improved mitochondrial function and lowered tBHP-induced apoptosis, necrosis, and ROS production. Activation of MAPK by tBHP was significantly suppressed by both drugs. Physically injured IVDs were treated immediately after transection with Amo or NAC for 24 hours, and then stained with dihydroethidium (DHE), a fluorescent probe for ROS production. Immunofluorescence was used to track the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a transcription factor that induces the expression of antioxidant genes. Amo and NAC significantly reduced ROS production and increased Nrf2 expression.

Conclusion: These findings suggest that the progression of IDD may be forestalled by Amo via protection of NP cells from oxidative stress following IVD injury.

Clinical Significance: This study will define the extent to which a novel, minimally invasive procedure targeting oxidative stress in NP cells can augment surgical interventions intended to retard IVD degeneration.
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http://dx.doi.org/10.1016/j.spinee.2021.02.008DOI Listing
June 2021

Accumulation of Contaminants by Wild Turkeys and Potential for Consumer Exposure.

Environ Toxicol Chem 2021 Apr 10;40(4):1222-1231. Epub 2021 Mar 10.

Savannah River Ecology Laboratory, Warnell School of Forestry and Natural Resources, University of Georgia, Aiken, South Carolina, USA.

Despite their popularity as a game species across North America, little is known about contaminant burdens in wild turkeys (Meleagris gallopavo) inhabiting areas of environmental contamination, and their potential to expose human and wildlife consumers. We compared trace element concentrations and radionuclide activity in muscle and liver tissues of turkeys inhabiting the Savannah River Site (USA), an area with known anthropogenic contaminant inputs, with turkeys from uncontaminated areas offsite. In addition, we tested breast feathers from a subset of individuals for mercury (Hg) to assess the viability of nonlethal sampling for quantifying Hg concentrations. Finally, we quantified arsenic, Hg, and selenium (Se) in blood of live-captured turkeys inhabiting a coal ash basin on the Savannah River Site. Compared with reference samples, we found that turkeys inhabiting the Savannah River Site contained elevated Hg levels in both muscle and liver tissues, and lower concentrations of chromium. Turkeys from the ash basin also had elevated levels of Se. We found a positive correlation between breast muscle and feather Hg concentrations (F  = 267.5, R  = 0.82, p < 0.001), suggesting that feathers can potentially be used as a nonlethal sampling technique. All elements analyzed were below reference limits set by the Centers for Disease Control and Prevention for safe consumption. Thus, our data suggest that turkeys likely are not an important pathway of contaminant exposure on the Savannah River Site or other areas with similar contaminant distributions. Environ Toxicol Chem 2021;40:1222-1231. © 2020 SETAC.
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http://dx.doi.org/10.1002/etc.4967DOI Listing
April 2021

Behavioral strategies during incubation influence nest and female survival of Wild Turkeys.

Ecol Evol 2020 Oct 24;10(20):11752-11765. Epub 2020 Sep 24.

Warnell School of Forestry and Natural Resources University of Georgia Athens GA USA.

Females must balance physiological and behavioral demands of producing offspring with associated expenditures, such as resource acquisition and predator avoidance. Nest success is an important parameter underlying avian population dynamics. Galliforms are particularly susceptible to low nest success due to exposure of ground nests to multiple predator guilds, lengthy incubation periods, and substantive reliance on crypsis for survival. Hence, it is plausible that nesting individuals prioritize productivity and survival differently, resulting in a gradient of reproductive strategies. Fine-scale movement patterns during incubation are not well documented in ground-nesting birds, and the influence of reproductive movements on survival is largely unknown. Using GPS data collected from female wild turkeys ( = 278) across the southeastern United States, we evaluated the influence of incubation recess behaviors on trade-offs between nest and female survival. We quantified daily recess behaviors including recess duration, recess frequency, total distance traveled, and incubation range size for each nest attempt as well as covariates for nest concealment, nest attempt, and nest age. Of 374 nests, 91 (24%) hatched and 39 (14%) females were depredated during incubation. Average nest survival during the incubation period was 0.19, whereas average female survival was 0.78. On average, females took 1.6 daily unique recesses ( = 1.2), spent 2.1 hr off the nest each day ( = 1.8), and traveled 357.6 m during recesses ( = 396.6). Average nest concealment was 92.5 cm ( = 47). We found that females who took longer recess bouts had higher individual survival, but had increased nest loss. Females who recessed more frequently had lower individual survival. Our findings suggest behavioral decisions made during incubation represent life-history trade-offs between predation risk and reproductive success on an unpredictable landscape.
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http://dx.doi.org/10.1002/ece3.6812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593161PMC
October 2020

Anopheline and human drivers of malaria risk in northern coastal, Ecuador: a pilot study.

Malar J 2020 Oct 2;19(1):354. Epub 2020 Oct 2.

Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN, 46556, USA.

Background: Understanding local anopheline vector species and their bionomic traits, as well as related human factors, can help combat gaps in protection.

Methods: In San José de Chamanga, Esmeraldas, at the Ecuadorian Pacific coast, anopheline mosquitoes were sampled by both human landing collections (HLCs) and indoor-resting aspirations (IAs) and identified using both morphological and molecular methods. Human behaviour observations (HBOs) (including temporal location and bed net use) were documented during HLCs as well as through community surveys to determine exposure to mosquito bites. A cross-sectional evaluation of Plasmodium falciparum and Plasmodium vivax infections was conducted alongside a malaria questionnaire.

Results: Among 222 anopheline specimens captured, based on molecular analysis, 218 were Nyssorhynchus albimanus, 3 Anopheles calderoni (n = 3), and one remains unidentified. Anopheline mean human-biting rate (HBR) outdoors was (13.69), and indoors (3.38) (p = 0.006). No anophelines were documented resting on walls during IAs. HBO-adjusted human landing rates suggested that the highest risk of being bitten was outdoors between 18.00 and 20.00 h. Human behaviour-adjusted biting rates suggest that overall, long-lasting insecticidal bed nets (LLINs) only protected against 13.2% of exposure to bites, with 86.8% of exposure during the night spent outside of bed net protection. The malaria survey found 2/398 individuals positive for asymptomatic P. falciparum infections. The questionnaire reported high (73.4%) bed net use, with low knowledge of malaria.

Conclusion: The exophagic feeding of anopheline vectors in San Jose de Chamanga, when analysed in conjunction with human behaviour, indicates a clear gap in protection even with high LLIN coverage. The lack of indoor-resting anophelines suggests that indoor residual spraying (IRS) may have limited effect. The presence of asymptomatic infections implies the presence of a human reservoir that may maintain transmission.
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http://dx.doi.org/10.1186/s12936-020-03426-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532652PMC
October 2020

Quantifying the Relationship between Conformational Dynamics and Enzymatic Activity in Ribonuclease HI Homologues.

Biochemistry 2020 09 24;59(35):3201-3205. Epub 2020 Aug 24.

Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, United States.

Ribonuclease HI (RNHI), a ubiquitous, non-sequence-specific endonuclease, cleaves the RNA strand in RNA/DNA hybrids. RNHI functions in replication and genome maintenance, and retroviral reverse transcriptases contain an essential ribonuclease H domain. Nuclear magnetic resonance (NMR) spectroscopy combined with molecular dynamics (MD) simulations suggests a model in which the extended handle region domain of RNHI populates (substrate-binding-competent) "open" and (substrate-binding-incompetent) "closed" states, while the thermophilic RNHI mainly populates the closed state at 300 K [Stafford, K. A., Robustelli, P., and Palmer, A. G., III (2013) , 1-10]. In addition, an -designed mutant Val98Ala RNHI was predicted to populate primarily the closed state. The work presented here validates this model and confirms the predicted properties of the designed mutant. MD simulations suggest that the conformational preferences of the handle region correlate with the conformations of Trp85, Thr92, and Val101. NMR residual dipolar coupling constants, three-bond scalar coupling constants, and chemical shifts experimentally define the conformational states of these residues and hence of the handle domain. These NMR parameters correlate with the Michaelis constants for RNHI homologues, confirming the important role of the handle region in the modulation of substrate recognition and illustrating the power of NMR spectroscopy in dissecting the conformational preferences underlying enzyme function.
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http://dx.doi.org/10.1021/acs.biochem.0c00500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737441PMC
September 2020

Validation of a noninvasive technique to quantify stress in northern bobwhite ().

Conserv Physiol 2020 13;8(1):coaa026. Epub 2020 Apr 13.

D. B. Warnell School of Forestry and Natural Resources, University of Georgia, Athens, GA, 30602, USA.

Examination of the endocrine system through non-invasive fecal sampling may improve population management more than using demographic indicators alone. By addressing the physiological mechanisms that are influencing fitness, management actions can be proactively developed to alleviate stressors. Proactive determination of vulnerable populations is critical for species of concern, such as the Northern Bobwhite (), which have suffered decades of population decline. We validated an assay to noninvasively measure the adrenocortical response of captive reared bobwhite through fecal corticosterone metabolites (FCM). All individuals received three sequential 48-hour treatments in which samples were collected every 4 hours, including a reference period, an adrenocorticotropic hormone (ACTH) challenge and a biological stressor (exposure to a hunting dog). Reference FCM values had a mean concentration of 16.75 pg/mg (95% CrI: 13.68, 19.91) with adrenocortical activity increasing by 73% for the duration of the ACTH challenge (29.00 pg/mg; CrI: 25.01, 33.78). FCM concentrations remained similar to that of the reference levels during the biological stressor (16.56 pg/mg; CrI: 13.33, 19.92). Our study validates the use of feces to detect changes in FCM levels in our subject species but also demonstrates the complexity of FCM and the importance of both physiological and biological validation prior to field implementation.
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http://dx.doi.org/10.1093/conphys/coaa026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154183PMC
April 2020

Targeting Cell Contractile Forces: A Novel Minimally Invasive Treatment Strategy for Fibrosis.

Ann Biomed Eng 2020 Jun 31;48(6):1850-1862. Epub 2020 Mar 31.

University of Iowa, Iowa City, IA, 52242, USA.

Fibrosis is a complication of tendon injury where excessive scar tissue accumulates in and around the injured tissue, leading to painful and restricted joint motion. Unfortunately, fibrosis tends to recur after surgery, creating a need for alternative approaches to disrupt scar tissue. We posited a strategy founded on mechanobiological principles that collagen under tension generated by fibroblasts is resistant to degradation by collagenases. In this study, we tested the hypothesis that blebbistatin, a drug that inhibits cellular contractile forces, would increase the susceptibility of scar tissue to collagenase degradation. Decellularized tendon scaffolds (DTS) were treated with bacterial collagenase with or without external or cell-mediated internal tension. External tension producing strains of 2-4% significantly reduced collagen degradation compared with non-tensioned controls. Internal tension exerted by human fibroblasts seeded on DTS significantly reduced the area of the scaffolds compared to acellular controls and inhibited collagen degradation compared to free-floating DTS. Treatment of cell-seeded DTS with 50 mM blebbistatin restored susceptibility to collagenase degradation, which was significantly greater than in untreated controls (p < 0.01). These findings suggest that therapies combining collagenases with drugs that reduce cell force generation should be considered in cases of tendon fibrosis that do not respond to physiotherapy.
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http://dx.doi.org/10.1007/s10439-020-02497-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286797PMC
June 2020

Phylogenetic debugging of a complete human biosynthetic pathway transplanted into yeast.

Nucleic Acids Res 2020 01;48(1):486-499

Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY, USA.

Cross-species pathway transplantation enables insight into a biological process not possible through traditional approaches. We replaced the enzymes catalyzing the entire Saccharomyces cerevisiae adenine de novo biosynthesis pathway with the human pathway. While the 'humanized' yeast grew in the absence of adenine, it did so poorly. Dissection of the phenotype revealed that PPAT, the human ortholog of ADE4, showed only partial function whereas all other genes complemented fully. Suppressor analysis revealed other pathways that play a role in adenine de-novo pathway regulation. Phylogenetic analysis pointed to adaptations of enzyme regulation to endogenous metabolite level 'setpoints' in diverse organisms. Using DNA shuffling, we isolated specific amino acids combinations that stabilize the human protein in yeast. Thus, using adenine de novo biosynthesis as a proof of concept, we suggest that the engineering methods used in this study as well as the debugging strategies can be utilized to transplant metabolic pathway from any origin into yeast.
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http://dx.doi.org/10.1093/nar/gkz1098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145547PMC
January 2020

Severe chorioretinal atrophy in Boucher-Neuhauser syndrome.

Can J Ophthalmol 2020 02 9;55(1):e26-e28. Epub 2019 Aug 9.

Hamilton Regional Eye Institute, Division of Ophthalmology, Department of Surgery, McMaster University, Hamilton, Ont.. Electronic address:

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http://dx.doi.org/10.1016/j.jcjo.2019.07.001DOI Listing
February 2020

Sulfasalazine Resolves Joint Stiffness in a Rabbit Model of Arthrofibrosis.

J Orthop Res 2020 03 11;38(3):629-638. Epub 2019 Nov 11.

Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa, Iowa City, Iowa, 52242.

Joint stiffness due to fibrosis/capsule contracture is a seriously disabling complication of articular injury that surgical interventions often fail to completely resolve. Fibrosis/contracture is associated with the abnormal persistence of myofibroblasts, which over-produce and contract collagen matrices. We hypothesized that intra-articular therapy with drugs targeting myofibroblast survival (sulfasalazine), or collagen production (β-aminopropionitrile and cis-hydroxyproline), would reduce joint stiffness in a rabbit model of fibrosis/contracture. Drugs were encapsulated in poly[lactic-co-glycolic] acid pellets and implanted in joints after fibrosis/contracture induction. Capsule α-smooth muscle actin (α-SMA) expression and intimal thickness were evaluated by immunohistochemistry and histomorphometry, respectively. Joint stiffness was quantified by flexion-extension testing. Drawer tests were employed to determine if the drugs induced cruciate ligament laxity. Joint capsule fibroblasts were tested in vitro for contractile activity and α-SMA expression. Stiffness in immobilized joints treated with blank pellets (control) was significantly higher than in non-immobilized, untreated joints (normal) (p = 0.0008), and higher than in immobilized joints treated with sulfasalazine (p = 0.0065). None of the drugs caused significant cruciate ligament laxity. Intimal thickness was significantly lower than control in the normal and sulfasalazine-treated groups (p = 0.010 and 0.025, respectively). Contractile activity in the cells from controls was significantly increased versus normal (p = 0.001). Sulfasalazine and β-aminopropionitrile significantly inhibited this effect (p = 0.005 and 0.0006, respectively). α-SMA expression was significantly higher in control versus normal (p = 0.0021) and versus sulfasalazine (p = 0.0007). These findings support the conclusion that sulfasalazine reduced stiffness by clearing myofibroblasts from fibrotic joints. Statement of clinical significance: The results provide proof-of-concept that established joint stiffness can be resolved non-surgically. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:629-638, 2020.
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http://dx.doi.org/10.1002/jor.24499DOI Listing
March 2020

Nonconsumptive effects of hunting on a nontarget game bird.

Ecol Evol 2019 Aug 30;9(16):9324-9333. Epub 2019 Jul 30.

D. B. Warnell School of Forestry and Natural Resources University of Georgia Athens GA USA.

Human hunting activity and disturbance can significantly impact prey species through both consumptive and nonconsumptive effects. The nonconsumptive effects of rabbit hunting on Northern Bobwhite (; hereafter, bobwhite) are currently unknown. Increased perceived risk of predation by bobwhite during rabbit hunting events may elicit antipredator responses among bobwhite that impact fitness via changes in behavior that ultimately impact population growth.We estimated the nonconsumptive effects of rabbit hunting on bobwhite behavior using telemetry across varying rabbit hunting intensities. Movements were analyzed using Bayesian hierarchical modeling with a before-after-control-impact (BACI) design to determine the effect of rabbit hunting on bobwhite.We observed an overall reduction in bobwhite movement in the presence of rabbit hunting, with a 38% (Posterior Overlap = 0.01) increase in bobwhite step length in the absence of rabbit hunting. We also observed bobwhite maintaining closer proximity to hardwood and escape cover under high rabbit hunting intensity, with a 59% (Posterior Overlap = 0.03) increase in distance from hardwood and a 28% (Posterior Overlap = 0.14) increase in distance from escape cover when rabbit hunting was removed. . Heightened antipredator behavior through decreased movement may assist with bobwhite predator avoidance. However, decreased movement and increased use of poor habitats may also have negative effects as a result of reduced foraging time or increased susceptibility to other predators. Future research should attempt to quantify the effect of decreased movement on bobwhite fitness through the evaluation of foraging time and survival in order to continue to improve management efforts for the species.
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http://dx.doi.org/10.1002/ece3.5479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706207PMC
August 2019

Combined branch retinal artery and branch retinal vein occlusion from a globe penetrating nail gun injury.

GMS Ophthalmol Cases 2019 18;9:Doc24. Epub 2019 Jun 18.

Department of Eye Medicine & Surgery, McMaster University & St. Joseph's Healthcare, Hamilton, Ontario, Canada.

Nail gun injuries represent a significant proportion of work-related ocular trauma. Here we report a rare case of a combined branch retinal arterial occlusion (BRAO) and branch retinal venous occlusion (BRVO) from a nail gun injury in a patient who was wearing eye protection. A 23-year-old male presented with a left globe penetrating injury from a pneumatic nail gun. The nail ricochet bypassed the patient's protective eyewear, penetrating the left globe causing multiple retinal tears and a combined BRAO and BRVO in the inferior temporal vascular arcade. The patient underwent prompt surgical repair obtaining an excellent anatomic outcome. However, the visual outcome was 20/200 OS at one and two years post injury primarily due to extensive ischemic damage of the retina. This case is the first to describe a combined BRAO and BRVO from a globe penetrating injury. What makes this case even rarer is that the patient was wearing eye protection at the time of the injury. Despite appropriate emergency management, rapid referral for ophthalmologist assessment, and timely surgical management of this patient, the visual outcome was poor. The vascular injury ultimately compromised a significant segment of the retina, including the macula.
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http://dx.doi.org/10.3205/oc000113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637433PMC
June 2019

Machine learning of large-scale spatial distributions of wild turkeys with high-dimensional environmental data.

Ecol Evol 2019 May 24;9(10):5938-5949. Epub 2019 Apr 24.

Mississippi Forestry Association Jackson Mississippi.

Species distribution modeling often involves high-dimensional environmental data. Large amounts of data and multicollinearity among covariates impose challenges to statistical models in variable selection for reliable inferences of the effects of environmental factors on the spatial distribution of species. Few studies have evaluated and compared the performance of multiple machine learning (ML) models in handling multicollinearity. Here, we assessed the effectiveness of removal of correlated covariates and regularization to cope with multicollinearity in ML models for habitat suitability. Three machine learning algorithms maximum entropy (MaxEnt), random forests (RFs), and support vector machines (SVMs) were applied to the original data (OD) of 27 landscape variables, reduced data (RD) with 14 highly correlated covariates being removed, and 15 principal components (PC) of the OD accounting for 90% of the original variability. The performance of the three ML models was measured with the area under the curve and continuous Boyce index. We collected 663 nonduplicated presence locations of Eastern wild turkeys () across the state of Mississippi, United States. Of the total locations, 453 locations separated by a distance of ≥2 km were used to train the three ML algorithms on the OD, RD, and PC data, respectively. The remaining 210 locations were used to validate the trained ML models to measure ML performance. Three ML models had excellent performance on the RD and PC data. MaxEnt and SVMs had good performance on the OD data, indicating the adequacy of regularization of the default setting for multicollinearity. Weak learning of RFs through bagging appeared to alleviate multicollinearity and resulted in excellent performance on the OD data. Regularization of ML algorithms may help exploratory studies of the effects of environmental factors on the spatial distribution and habitat suitability of wildlife.
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http://dx.doi.org/10.1002/ece3.5177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540709PMC
May 2019

Looking back on wartime service: Reminiscence by James G. Van Straten.

Aging Ment Health 2019 09 6;23(9):1067-1073. Epub 2019 May 6.

b University of Alabama , Tuscaloosa , Alabama , USA.

In this article we highlight the reminiscence of a distinguished Veteran of the Vietnam War. The narrative describes his wartime service in Vietnam and the legacy of these experiences across his military career and subsequent civilian life. The individual profiled is not intended to represent all Veterans who served in the Vietnam War. In fact, this is a very unique individual; a highly educated, career officer and committed Catholic who served in various roles within the United States Army Medical Department. This narrative represents memories and reflections from his military career and in his subsequent post-military civilian life.
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http://dx.doi.org/10.1080/13607863.2019.1609904DOI Listing
September 2019

Intraspecific temporal resource partitioning at white-tailed deer feeding sites.

Curr Zool 2019 Apr 6;65(2):139-146. Epub 2018 Jul 6.

Warnell School of Forestry and Natural Resources, University of Georgia, Athens, GA, USA.

Individuals may reduce competition by temporally partitioning their use of a shared resource. Behavioral differences between sexes in ungulates may encourage segregation as individuals attempt to avoid antagonistic interactions. However, dominant sex and age groups may reduce subordinates' access to food resources, regardless of the subordinate's sex. We hypothesized that white-tailed deer temporally segregated at supplemental feeding sites based on social rank (subordinate: yearling males and adult females; dominant: adult males) and that segregation was affected by phase of the breeding season and diel cycle. If deer temporally segregate according to social rank, we predicted that the resulting activity patterns would manifest in one social class being relatively more susceptible to hunter-induced mortality. We used a multi-state modeling approach to quantify temporal segregation and calculated the probability that a feeding site was in a particular state during diurnal and nocturnal hours for each of the 3 phases of the breeding season. We determined that transition probabilities differed by season and diel cycle and dominant and subordinate social classes clearly avoided each other, with <1% co-occurrence at feeding sites. During the pre-breeding season, the probability of a subordinate being present during diurnal hours was 3.0 more likely than a dominant being present, but did not differ during nocturnal hours. There was no difference for dominants and subordinates during diurnal or nocturnal hours during the breeding season. In the post-breeding season, subordinates were 1.7 more likely to occur at the feeding site than a dominant during diurnal hours but they did not differ during nocturnal hours. Our results indicate that dominance status influences temporal segregation at feeding sites and is affected by the phase of the breeding season. Therefore, the resulting activity patterns may increase subordinates' risk to human predation during the pre-breeding and post-breeding seasons.
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http://dx.doi.org/10.1093/cz/zoy051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430969PMC
April 2019

Tissue Engineering for the Temporomandibular Joint.

Adv Healthc Mater 2019 01 17;8(2):e1801236. Epub 2018 Dec 17.

Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, 52242, USA.

Tissue engineering potentially offers new treatments for disorders of the temporomandibular joint which frequently afflict patients. Damage or disease in this area adversely affects masticatory function and speaking, reducing patients' quality of life. Effective treatment options for patients suffering from severe temporomandibular joint disorders are in high demand because surgical options are restricted to removal of damaged tissue or complete replacement of the joint with prosthetics. Tissue engineering approaches for the temporomandibular joint are a promising alternative to the limited clinical treatment options. However, tissue engineering is still a developing field and only in its formative years for the temporomandibular joint. This review outlines the anatomical and physiological characteristics of the temporomandibular joint, clinical management of temporomandibular joint disorder, and current perspectives in the tissue engineering approach for the temporomandibular joint disorder. The tissue engineering perspectives have been categorized according to the primary structures of the temporomandibular joint: the disc, the mandibular condyle, and the glenoid fossa. In each section, contemporary approaches in cellularization, growth factor selection, and scaffold fabrication strategies are reviewed in detail along with their achievements and challenges.
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http://dx.doi.org/10.1002/adhm.201801236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075314PMC
January 2019

Impacts of biomass production at civil airports on grassland bird conservation and aviation strike risk.

Ecol Appl 2018 07 7;28(5):1168-1181. Epub 2018 May 7.

Warnell School of Forestry and Natural Resources, Savannah River Ecology Lab, University of Georgia, Athens, Georgia, 30602, USA.

Growing concerns about climate change, foreign oil dependency, and environmental quality have fostered interest in perennial native grasses (e.g., switchgrass [Panicum virgatum]) for bioenergy production while also maintaining biodiversity and ecosystem function. However, biomass cultivation in marginal landscapes such as airport grasslands may have detrimental effects on aviation safety as well as conservation efforts for grassland birds. In 2011-2013, we investigated effects of vegetation composition and harvest frequency on seasonal species richness and habitat use of grassland birds and modeled relative abundance, aviation risk, and conservation value of birds associated with biomass crops. Avian relative abundance was greater in switchgrass monoculture plots during the winter months, whereas Native Warm-Season Grass (NWSG) mixed species plantings were favored by species during the breeding season. Conversely, treatment differences in aviation risk and conservation value were not biologically significant. Only 2.6% of observations included avian species of high hazard to aircraft, providing support for semi-natural grasslands as a feasible landcover option at civil airports. Additionally, varied harvest frequencies across a mosaic of switchgrass monocultures and NWSG plots allows for biomass production with multiple vegetation structure options for grassland birds to increase seasonal avian biodiversity and habitat use.
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http://dx.doi.org/10.1002/eap.1716DOI Listing
July 2018

Effects of knockout of the receptor for advanced glycation end-products on bone mineral density and synovitis in mice with intra-articular fractures.

J Orthop Res 2018 09 24;36(9):2439-2449. Epub 2018 May 24.

Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242.

Our group employed the mouse closed intra-articular fracture (IAF) model to test the hypothesis that the innate immune system plays a role in initiating synovitis and post-traumatic osteoarthritis (PTOA) in fractured joints. A transgenic strategy featuring knockout of the receptor for advanced glycation end-products (RAGE ) was pursued. The 42 and 84 mJ impacts used to create fractures were in the range previously reported to cause PTOA at 60 days post-fracture. MicroCT (μCT) was used to assess fracture patterns and epiphyseal and metaphyseal bone loss at 30 and 60 days post-fracture. Cartilage degeneration, synovitis, and matrix metalloproteinase (MMP-3, -13) expression were evaluated by histologic analyses. In wild-type mice, μCT imaging showed that 84 mJ impacts led to significant bone loss at 30 days (p < 0.05), but recovered to normal at 60 days. Bone losses did not occur in RAGE mice. Synovitis was significantly elevated in 84 mJ impact wild-type mice at both endpoints (30 day, p = 0.001; 60 day, p = 0.05), whereas in RAGE mice synovitis was elevated only at 30 days (p = 0.02). Mankin scores were slightly elevated in both mouse strains at 30 days, but not at 60 days. Immunohistochemistry revealed significant fracture-related increases in MMP-3 and -13 expression at 30 days (p < 0.05), with no significant difference between genotypes. These findings indicated that while RAGE accelerated recovery from fracture and diminished synovitis, arthritic changes were temporary and too modest to detect an effect on the pathogenesis of PTOA. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2439-2449, 2018.
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http://dx.doi.org/10.1002/jor.24021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128287PMC
September 2018

Targeting mitochondrial responses to intra-articular fracture to prevent posttraumatic osteoarthritis.

Sci Transl Med 2018 02;10(427)

University of Iowa, Iowa City, IA 52242, USA.

We tested whether inhibiting mechanically responsive articular chondrocyte mitochondria after severe traumatic injury and preventing oxidative damage represent a viable paradigm for posttraumatic osteoarthritis (PTOA) prevention. We used a porcine hock intra-articular fracture (IAF) model well suited to human-like surgical techniques and with excellent anatomic similarities to human ankles. After IAF, amobarbital or -acetylcysteine (NAC) was injected to inhibit chondrocyte electron transport or downstream oxidative stress, respectively. Effects were confirmed via spectrophotometric enzyme assays or glutathione/glutathione disulfide assays and immunohistochemical measures of oxidative stress. Amobarbital or NAC delivered after IAF provided substantial protection against PTOA at 6 months, including maintenance of proteoglycan content, decreased histological disease scores, and normalized chondrocyte metabolic function. These data support the therapeutic potential of targeting chondrocyte metabolism after injury and suggest a strong role for mitochondria in mediating PTOA.
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http://dx.doi.org/10.1126/scitranslmed.aan5372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987523PMC
February 2018

Ultrasound-Mediated Microbubble Destruction Suppresses Melanoma Tumor Growth.

Ultrasound Med Biol 2018 04 1;44(4):831-839. Epub 2018 Feb 1.

Department of Orthopaedics and Rehabilitation, The University of Iowa, Iowa City, Iowa, USA.

Melanoma is one of the most aggressive types of cancer, and its incidence has increased rapidly in the past few decades. In this study, we investigated a novel treatment approach, the use of low-intensity ultrasound (2.3 W/cm at 1 MHz)-mediated Optison microbubble (MB) destruction (UMMD) to treat melanoma in a flank tumor model. The effect of UMMD was first evaluated in the melanoma cell line B16 F10 (B16) in vitro and then in mice inoculated with B16 cells. MBB16 cells were exposed to US in vitro, resulting in significant cell death proportional to duty cycle (R = 0.74): approximately 30%, 50%, 80% and 80% cell death at 10%, 30%, 50% and 100% DC respectively. Direct implantation of tumors with MBs, followed by sonication, resulted in retarded tumor growth and improved survival (p = 0.0106). Immunohistochemical analyses confirmed the significant changes in expression of the cell proliferation marker Ki67 (p = 0.037) and a microtubule-associated protein 2 (p = 0.048) after US + MB treatment. These results suggest that UMMD could be used as a possible treatment approach in isolated melanoma and has the potential to translate to clinical trials.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2017.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826859PMC
April 2018

Combining ultrasound and intratumoral administration of doxorubicin-loaded microspheres to enhance tumor cell killing.

Int J Pharm 2018 Mar 17;539(1-2):139-146. Epub 2018 Jan 17.

Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa, IA, USA. Electronic address:

Melanoma is an incurable disease for which alternative treatments to chemotherapy alone are sought. Here, using a melanoma model, we investigated the antitumor potential of combining ultrasound (US) with poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with doxorubicin (DOX). The aim was to achieve synergistic tumoricidal activity through direct and indirect US-mediated damage of tumor cells combined with sustained and potentially controllable release (when combined with US) of DOX from microspheres. An in vitro release assay demonstrated an ability of US to affect the release kinetics of DOX from DOX-loaded PLGA microspheres by inducing a 12% increase in the rate of release. In vitro viability assays demonstrated that combining US with DOX-loaded PLGA microspheres resulted in synergistic tumor cell (B16-F10 melanoma cells) killing. Melanoma-bearing mice were treated intratumorally with DOX (8 µg)-loaded microspheres and subjected to US treatment at the tumor site. This treatment could significantly extend survival (mean survival (MS) = 22.1 days) compared to untreated mice (MS = 10.4 days) and most other treatments, such as blank microspheres plus US (MS = 11.5 days) and DOX (8 µg)-loaded microspheres alone (MS = 13 days). The findings that immune checkpoint blockade did not significantly extend survival of mice treated with DOX (8 µg)-loaded microspheres plus US, and that tumor-free ("cured") mice were not protected from subsequent tumor rechallenge suggests minimal involvement of the adaptive immune response in the observed antitumor activity. Nevertheless, the synergistic increase in survival of melanoma-challenged mice treated with the combination of US and DOX-loaded microspheres implicates such a treatment methodology as a promising additional tool for combatting otherwise currently incurable cancers.
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http://dx.doi.org/10.1016/j.ijpharm.2018.01.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372090PMC
March 2018

Ultrasound-triggered PLGA microparticle destruction and degradation for controlled delivery of local cytotoxicity and drug release.

Int J Biol Macromol 2018 Jan 26;106:1211-1217. Epub 2017 Aug 26.

Department of Dental Materials, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea. Electronic address:

In this study, we investigated the low intensity ultrasound (US)-controlled delivery of local cytotoxicity and drug release via induced destruction and degradation of microparticles (MPs) made of poly(lactic-co-glycolic acid) (PLGA). This study was conducted in vitro with potential application towards tumor treatment in conjunction with direct injection. MPs, either loaded with or without doxorubicin (DOX), were prepared using a double-emulsion solvent-evaporation technique. First, the MPs were exposed to US with duty cycle (DC)-modulation. The destruction and degradation of MPs were evaluated using light and scanning electron microscopy. Second, the effects of US-mediated destruction/degradation of MPs on the local cytotoxicity as well as DOX release were evaluated. US-triggered MP destruction/degradation significantly enhanced nearby cell death and DOX release. These affects occurred in proportion to the DC. Our findings indicate that controlled cytotoxicity and DOX release by US could be useful in developing the minimally invasive therapeutic applications for tumor treatment.
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http://dx.doi.org/10.1016/j.ijbiomac.2017.08.125DOI Listing
January 2018

DAMPs Synergize with Cytokines or Fibronectin Fragment on Inducing Chondrolysis but Lose Effect When Acting Alone.

Mediators Inflamm 2017 18;2017:2642549. Epub 2017 Jul 18.

Department of Orthopaedics and Rehabilitation, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.

Objective And Design: To investigate whether endogenous damage-associated molecular patterns (DAMPs) or alarmins originated from mitochondria or nucleus stimulates inflammatory response in articular chondrocytes to cause chondrolysis which leads to cartilage degradation featured in posttraumatic osteoarthritis (PTOA).

Materials: Primary cultures of bovine or human chondrocytes isolated from cartilage of weight-bearing joints.

Treatment: Chondrocytes were subjected to mitochondrial DAMPs (MTDs) or HMGB1, a nuclear DAMP (NuD), with or without the presence of an N-terminal 29 kDa fibronectin fragment (Fn-f) or proinflammatory cytokines (IL-1 and TNF-). Injured cartilage-conditioned culturing medium containing a mixture of DAMPs was employed as a control. After 24 hrs, the protein expression of cartilage degrading metalloproteinases and iNOS in culture medium or cell lysates was examined with Western blotting, respectively.

Results: HMGB1 was synergized with IL-1 in upregulating expression of MMP-3, MMP-13, ADAMTS-5, ADAM-8, and iNOS. Moreover, a moderate synergistic effect was detected between HMGB1 and Fn-f or between MTDs and TNF- on MMP-3 expression. However, when acting alone, MTDs or HMGB1 did not upregulate cartilage degrading enzymes or iNOS.

Conclusion: MTDs or HMGB1 could only stimulate inflammatory response in chondrocytes with the presence of cytokines or Fn-f.
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http://dx.doi.org/10.1155/2017/2642549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540522PMC
May 2018

Modeling the effect of blunt impact on mitochondrial function in cartilage: implications for development of osteoarthritis.

PeerJ 2017 17;5:e3468. Epub 2017 Jul 17.

Department of Orthopedics & Rehabilitation, University of Iowa, Iowa City, IA, United States of America.

Objective: Osteoarthritis (OA) is a disease characterized by degeneration of joint cartilage. It is associated with pain and disability and is the result of either age and activity related joint wear or an injury. Non-invasive treatment options are scarce and prevention and early intervention methods are practically non-existent. The modeling effort presented in this article is constructed based on an emerging biological hypothesis-post-impact oxidative stress leads to cartilage cell apoptosis and hence the degeneration observed with the disease. The objective is to quantitatively describe the loss of cell viability and function in cartilage after an injurious impact and identify the key parameters and variables that contribute to this phenomenon.

Methods: We constructed a system of differential equations that tracks cell viability, mitochondrial function, and concentrations of reactive oxygen species (ROS), adenosine triphosphate (ATP), and glycosaminoglycans (GAG). The system was solved using MATLAB and the equations' parameters were fit to existing data using a particle swarm algorithm.

Results: The model fits well the available data for cell viability, ATP production, and GAG content. Local sensitivity analysis shows that the initial amount of ROS is the most important parameter.

Discussion: The model we constructed is a viable method for producing in silico studies and with a few modifications, and data calibration and validation, may be a powerful predictive tool in the search for a non-invasive treatment for post-traumatic osteoarthritis.
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http://dx.doi.org/10.7717/peerj.3468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516774PMC
July 2017

Breeding chronology and social interactions affect ungulate foraging behavior at a concentrated food resource.

PLoS One 2017 7;12(6):e0178477. Epub 2017 Jun 7.

Warnell School of Forestry and Natural Resources, University of Georgia, Athens, Georgia, United States of America.

Prey species must balance predator avoidance behavior with other essential activities including foraging, breeding, and social interactions. Anti-predator behaviors such as vigilance can impede resource acquisition rates by altering foraging behavior. However, in addition to predation risk, foraging behavior may also be affected by socio-sexual factors including breeding chronology and social interactions. Therefore, we investigated how time-of-day, distance-to-forest, group size, social interactions (presence of different sex-age class), and breeding chronology (pre-breeding, breeding, post-breeding seasons) affected probability of feeding (hereafter: feeding) for different sex and age-classes (mature males, immature males, adult females, and juveniles) of white-tailed deer at feed sites. We developed a set of candidate models consisting of social, habitat, reproductive, and abiotic factors and combinations of these factors. We then used generalized linear mixed models (GLMMs) to estimate the probability of feeding and used model averaging of competing models for multimodel inference. Each adult sex-age class' feeding was influenced by breeding chronology. Juveniles were more likely to be feeding than adults in all seasons. Feeding increased with group size for all sex-age classes. The presence of a mature male negatively influenced the feeding of immature males and juveniles were more likely to be feeding when an adult female was present. Feeding decreased with increasing distance-to-forest for mature males but not for other sex-age classes. Our results indicate that each sex-age class modulates vigilance levels in response to socio-sexual factors according to the unique pressures placed upon them by their reproductive status and social rank.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0178477PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462360PMC
September 2017

Timing of nest vegetation measurement may obscure adaptive significance of nest-site characteristics: A simulation study.

Ecol Evol 2017 02 25;7(4):1259-1270. Epub 2017 Jan 25.

Warnell School of Forestry and Natural Resources Savannah River Ecology Lab University of Georgia Athens GA USA.

Advances in understanding avian nesting ecology are hindered by a prevalent lack of agreement between nest-site characteristics and fitness metrics such as nest success. We posit this is a result of inconsistent and improper timing of nest-site vegetation measurements. Therefore, we evaluated how the timing of nest vegetation measurement influences the estimated effects of vegetation structure on nest survival. We simulated phenological changes in nest-site vegetation growth over a typical nesting season and modeled how the timing of measuring that vegetation, relative to nest fate, creates bias in conclusions regarding its influence on nest survival. We modeled the bias associated with four methods of measuring nest-site vegetation: Method 1-measuring at nest initiation, Method 2-measuring at nest termination regardless of fate, Method 3-measuring at nest termination for successful nests and at estimated completion for unsuccessful nests, and Method 4-measuring at nest termination regardless of fate while also accounting for initiation date. We quantified and compared bias for each method for varying simulated effects, ranked models for each method using AIC, and calculated the proportion of simulations in which each model (measurement method) was selected as the best model. Our results indicate that the risk of drawing an erroneous or spurious conclusion was present in all methods but greater with Method 2 which is the most common method reported in the literature. Methods 1 and 3 were similarly less biased. Method 4 provided no additional value as bias was similar to Method 2 for all scenarios. While Method 1 is seldom practical to collect in the field, Method 3 is logistically practical and minimizes inherent bias. Implementation of Method 3 will facilitate estimating the effect of nest-site vegetation on survival, in the least biased way, and allow reliable conclusions to be drawn.
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http://dx.doi.org/10.1002/ece3.2767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5306001PMC
February 2017

Heavy metal bioaccumulation in two passerines with differing migration strategies.

Sci Total Environ 2017 Aug 12;592:25-32. Epub 2017 Mar 12.

University of Georgia, Warnell School of Forestry and Natural Resources, 180 E. Green St., Athens, GA 30602, USA; University of Georgia, Savannah River Ecology Laboratory, P.O. Drawer E, Aiken, SC 29803, USA. Electronic address:

Various anthropogenic activities have resulted in concentration of heavy metals and contamination of surrounding environments. Historically, heavy metal contamination at the Savannah River Site (SRS) in South Carolina has resulted from accidental releases of stored waste generated from nuclear weapon production in the early 1950s. Songbirds inhabiting and using resources from these areas have the potential to bioaccumulate metals but there is limited information on metal concentration levels in areas suspected of contamination as well as uncontaminated sites. Nonlethal tissues samples from avian blood and feathers provide a reliable approach for determining the bioavailability of these pollutants (As, Cd, Cr, Cu, Hg, Ni, Pb, Se, and Zn). The objectives of this study were to survey terrestrial heavy metal contamination at the SRS on potentially bioavailable contaminated (PBC) sites through blood and feather samples from resident Northern Cardinals (Cardinalis cardinalis) and migratory Great Crested Flycatchers (Myiarchus crinitus) and quantify sex-specific concentrations within species. Samples were collected in April to June of 2016. Cardinals had lower blood concentrations of Hg (β=-0.17, 85% CL=-0.26, -0.09) and Se (β=-0.33, 85% CL=-0.50, -0.16) than flycatchers. Cr feather concentrations were less in cardinals (β=-1.46, 85% CL=-2.44, -0.49) and all feathers of both species from reference locations had significantly less Zn (β=-67.92, 85% CL=-128.71, -7.14). Results indicate flycatchers were exposed to differing heavy metal levels during feather formation on their wintering grounds as compared to their recent exposure (through bloods samples) on their breeding grounds. Sex of individuals did not have a significant impact on bioaccumulation in either species. Overall, metal concentration levels in both species indicate minimal risk for acute toxicity; however, there is limited research on wild passerine populations with similar concentration levels. Therefore, further research on reproductive success of these birds should be explored.
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http://dx.doi.org/10.1016/j.scitotenv.2017.03.055DOI Listing
August 2017

Corneal endothelial cell loss after pars plana vitrectomy and combined phacoemulsification-vitrectomy surgeries.

Can J Ophthalmol 2017 Feb 1;52(1):4-8. Epub 2016 Oct 1.

St. Joseph's Healthcare Hamilton and McMaster University, Hamilton, Ont.

Objective: To compare postoperative corneal endothelial cell density (ECD) loss in eyes undergoing pars plana vitrectomy (PPV), or combination of cataract extraction (using phacoemulsification) and intraocular lens implantation with vitrectomy (CE/IOL-PPV) surgeries.

Methods: Institutional setting. Best-corrected visual acuity (BCVA) and ECD by specular microscopy were measured preoperatively and 3 months postoperatively in both groups. Relative postoperative ECD loss was the primary outcome measure. Change in BCVA was the secondary outcome measure.

Results: Forty eyes of 40 patients undergoing PPV and 46 eyes of 46 patients undergoing CE/IOL-PPV were included in the final analysis. Postoperative ECD was decreased slightly more in the CE/IOL-PPV group compared with the PPV group (13.9% ± 15.5% vs 9.0% ± 14.6%), although this was not statistically significant (p = 0.10). The improvement in the logMAR BCVA was, however, statistically more significant in the CE/IOL-PPV group compared with the PPV group (-56.6% ± 24.3% vs -38.6% ± 45.5%, p = 0.04).

Conclusions: PPV and the combination CE/IOL-PPV surgeries lead to modest and statistically similar postoperative decline in ECD. The combination surgery may lead to slightly more postoperative cells loss, but also more improvement in visual acuity.
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http://dx.doi.org/10.1016/j.jcjo.2016.06.001DOI Listing
February 2017

Low escape-rate genome safeguards with minimal molecular perturbation of .

Proc Natl Acad Sci U S A 2017 02 7;114(8):E1470-E1479. Epub 2017 Feb 7.

Institute for Systems Genetics, New York University Langone Medical Center, New York, NY 10016;

As the use of synthetic biology both in industry and in academia grows, there is an increasing need to ensure biocontainment. There is growing interest in engineering bacterial- and yeast-based safeguard (SG) strains. First-generation SGs were based on metabolic auxotrophy; however, the risk of cross-feeding and the cost of growth-controlling nutrients led researchers to look for other avenues. Recent strategies include bacteria engineered to be dependent on nonnatural amino acids and yeast SG strains that have both transcriptional- and recombinational-based biocontainment. We describe improving yeast -based transcriptional SG strains, which have near-WT fitness, the lowest possible escape rate, and nanomolar ligands controlling growth. We screened a library of essential genes, as well as the best-performing promoter and terminators, yielding the best SG strains in yeast. The best constructs were fine-tuned, resulting in two tightly controlled inducible systems. In addition, for potential use in the prevention of industrial espionage, we screened an array of possible "decoy molecules" that can be used to mask any proprietary supplement to the SG strain, with minimal effect on strain fitness.
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http://dx.doi.org/10.1073/pnas.1621250114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338387PMC
February 2017