A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart.

Cardiomyocytes are subjected to the intense mechanical stress and metabolic demands of the beating heart. It is unclear whether these cells, which are long-lived and rarely renew, manage to preserve homeostasis on their own. While analyzing macrophages lodged within the healthy myocardium, we discovered that they actively took up material, including mitochondria, derived from cardiomyocytes. Cardiomyocytes ejected dysfunctional mitochondria and other cargo in dedicated membranous particles reminiscent of neural exophers, through a process driven by the cardiomyocyte's autophagy machinery that was enhanced during cardiac stress. Depletion of cardiac macrophages or deficiency in the phagocytic receptor Mertk resulted in defective elimination of mitochondria from the myocardial tissue, activation of the inflammasome, impaired autophagy, accumulation of anomalous mitochondria in cardiomyocytes, metabolic alterations, and ventricular dysfunction. Thus, we identify an immune-parenchymal pair in the murine heart that enables transfer of unfit material to preserve metabolic stability and organ function. VIDEO ABSTRACT.

Extracellular Kir2.1C122Y Mutant Upsets Kir2.1-PIP2 Bonds and Is Arrhythmogenic in Andersen-Tawil Syndrome.

BACKGROUND: Andersen-Tawil syndrome type 1 is a rare heritable disease caused by mutations in the gene coding the strong inwardly rectifying K+ channel Kir2.1. The extracellular Cys (cysteine)122-to-Cys154 disulfide bond in the channel structure is crucial for proper folding but has not been associated with correct channel function at the membrane. We evaluated whether a human mutation at the Cys122-to-Cys154 disulfide bridge leads to Kir2.1 channel dysfunction and arrhythmias by reorganizing the overall Kir2.1 channel structure and destabilizing its open state. METHODS: We identified a Kir2.1 loss-of-function mutation (c.366 A>T; p.Cys122Tyr) in an ATS1 family. To investigate its pathophysiological implications, we generated an AAV9-mediated cardiac-specific mouse model expressing the Kir2.1C122Y variant. We employed a multidisciplinary approach, integrating patch clamping and intracardiac stimulation, molecular biology techniques, molecular dynamics, and bioluminescence resonance energy transfer experiments. RESULTS: Kir2.1C122Y mice recapitulated the ECG features of ATS1 independently of sex, including corrected QT prolongation, conduction defects, and increased arrhythmia susceptibility. Isolated Kir2.1C122Y cardiomyocytes showed significantly reduced inwardly rectifier K+ (IK1) and inward Na+ (INa) current densities independently of normal trafficking. Molecular dynamics predicted that the C122Y mutation provoked a conformational change over the 2000-ns simulation, characterized by a greater loss of hydrogen bonds between Kir2.1 and phosphatidylinositol 4,5-bisphosphate than wild type (WT). Therefore, the phosphatidylinositol 4,5-bisphosphate-binding pocket was destabilized, resulting in a lower conductance state compared with WT. Accordingly, on inside-out patch clamping, the C122Y mutation significantly blunted Kir2.1 sensitivity to increasing phosphatidylinositol 4,5-bisphosphate concentrations. In addition, the Kir2.1C122Y mutation resulted in channelosome degradation, demonstrating temporal instability of both Kir2.1 and NaV1.5 proteins. CONCLUSIONS: The extracellular Cys122-to-Cys154 disulfide bond in the tridimensional Kir2.1 channel structure is essential for the channel function. We demonstrate that breaking disulfide bonds in the extracellular domain disrupts phosphatidylinositol 4,5-bisphosphate-dependent regulation, leading to channel dysfunction and defects in Kir2.1 energetic stability. The mutation also alters functional expression of the NaV1.5 channel and ultimately leads to conduction disturbances and life-threatening arrhythmia characteristic of Andersen-Tawil syndrome type 1.

p38γ is essential for cell cycle progression and liver tumorigenesis.

The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)-cyclin protein complex1. However, control of the G0-to-G1 transition is not completely understood. Here we demonstrate that p38 MAPK gamma (p38γ) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle. p38γ shares high sequence homology, inhibition sensitivity and substrate specificity with CDK family members. In mouse hepatocytes, p38γ induces proliferation after partial hepatectomy by promoting the phosphorylation of retinoblastoma tumour suppressor protein at known CDK target residues. Lack of p38γ or treatment with the p38γ inhibitor pirfenidone protects against the chemically induced formation of liver tumours. Furthermore, biopsies of human hepatocellular carcinoma show high expression of p38γ, suggesting that p38γ could be a therapeutic target in the treatment of this disease.

Mental health, subjective experiences and environmental change.

This article responds to Coope's call for the medical humanities to address the climate crisis as a health issue. Coope proposes three areas for progress towards ecological thinking in healthcare, with a focus on ecological mental health. The article emphasises the need to understand the cultural dimensions of mental health and proposes an interdisciplinary approach that integrates insights from the arts and humanities. It examines the impact of climate change on mental health, drawing on The Rockefeller Foundation - Lancet Commission on Planetary Health and recent studies. The discussion focuses on the intersection of mental health, subjective experience and environmental change. Focusing on emotional experiences as constructed from biological and cultural elements, the article proposes a holistic approach to mental health. It proposes two converging lines of research, in constant interaction: first, a historical and cultural research of those concepts, practices and symbols related to the environment, emphasising a cultural history of nature; and second, a synchronous research, drawing on anthropology, sociology and participatory art-based research, to understand how these aforementioned elements influence our current relations with nature. The article concludes by emphasising the urgency of developing narratives and histories that redirect temporal trajectories towards a better future, while respecting and acknowledging diverse narratives of individual experience. It calls for collaborative efforts from the medical humanities to contribute to a more comprehensive understanding of the complex relationship between mental health, nature and ecological crisis.

Assessment of visual function and the neuroretina in subjects diagnosed with congenital anomaly of color vision.

This cross-sectional and observational study includes 50 eyes of subjects with color blindness and 50 eyes of control subjects. Visual function (visual acuity, contrast sensitivity, and color vision) and neuroretinal structure were assessed in all subjects using optical coherence tomography (OCT). Significant thinning of the retinal nerve fiber layer, ganglion cell layer, and retina were observed in the color blindness group. Significant thinning was also recorded in layers that involve photoreceptor nuclei (between the outer limiting layer and the Bruch membrane and between the outer plexiform layer and the outer limiting membrane). OCT evaluation based on retinal segmentation is a rapid (5-10 minutes) non-invasive technique and seems to be a good biomarker of color blindness.

Beta-3 adrenergic receptor overexpression reverses aortic stenosis-induced heart failure and restores balanced mitochondrial dynamics.

Aortic stenosis (AS) is associated with left ventricular (LV) hypertrophy and heart failure (HF). There is a lack of therapies able to prevent/revert AS-induced HF. Beta3 adrenergic receptor (ß3AR) signaling is beneficial in several forms of HF. Here, we studied the potential beneficial effect of ß3AR overexpression on AS-induced HF. Selective ß3AR stimulation had a positive inotropic effect. Transgenic mice constitutively overexpressing human ß3AR in the heart (c-hß3tg) were protected from the development of HF in response to induced AS, and against cardiomyocyte mitochondrial dysfunction (fragmented mitochondria with remodeled cristae and metabolic reprogramming featuring altered substrate use). Similar beneficial effects were observed in wild-type mice inoculated with adeno-associated virus (AAV9) inducing cardiac-specific overexpression of human ß3AR before AS induction. Moreover, AAV9-hß3AR injection into wild-type mice at late disease stages, when cardiac hypertrophy and metabolic reprogramming are already advanced, reversed the HF phenotype and restored balanced mitochondrial dynamics, demonstrating the potential of gene-therapy-mediated ß3AR overexpression in AS. Mice with cardiac specific ablation of Yme1l (cYKO), characterized by fragmented mitochondria, showed an increased mortality upon AS challenge. AAV9-hß3AR injection in these mice before AS induction reverted the fragmented mitochondria phenotype and rescued them from death. In conclusion, our results step out that ß3AR overexpression might have translational potential as a therapeutic strategy in AS-induced HF.

Bioaccumulation of heavy metals and As in maize (Zea mays L) grown close to mine tailings strongly impacts plant development.

Potentially toxic metals and metalloids present in mining residues can affect ecosystems, particularly plant growth and development. In this study we evaluated heavy metal (Fe, Zn, Cu, Cd, Pb) and As contents in maize (Zea mays L) plants grown in soils collected near (40 m), at intermediate (400 m) and remote (3000 m) distances from mine tailings near Taxco City, Mexico. Soils sampled near and at intermediate sites from the tailings contained high levels of heavy metals which were 3- to 55-fold higher compared to the control samples. Heavy metal and As content in plants reflected the soil contamination being the greatest for most studied elements in root samples followed by stems, leaves, and kernels. Though plants were capable of completing their life cycle and producing the seeds, high bioaccumulation levels had a strong impact negatively on plant development. Abnormalities in the organs like malformations in reproductive structures (tassel and ear), reduction in the phytomer number and the plant height were present. Microscopic studies and morphometric analyses suggest that strongly affected plant growth result from negative and synergistic action of heavy metals and As in soils on cell growth and cell production. This study showed that maize grown near mine tailings accumulated high levels of heavy metals and As which decrease significantly plant yield and could be dangerous if it is consumed by animals and humans.

Measurement of sulfur in environmental samples using the interference standard method with an O2 -pressurized reaction cell and a single-quadrupole inductively coupled plasma mass spectrometer.

RATIONALE: Precise and accurate analysis of trace sulfur in environmental samples is essential to understand its biogeochemical cycle. Yet it remains a challenging analytical task for single-quadrupole inductively coupled plasma mass spectrometry (ICP-MS) instrumentation because of the presence of significant isobaric interferences. METHODS: We evaluated the effect that different instrumental parameters have on the formation of SO+ species, and show that, under our instrumental configuration, it is not possible to fully remove all spectral interferences. Consequently, our instrumental optimization is focused on minimizing their contribution while obtaining the best possible sensitivity. We assessed the performance of the interference standard (IFS) method, where the signal corresponding to the SO+ ions formed in the ICP is normalized to that of 36 Ar+ . RESULTS: We found that, by pressurizing the cell with O2 , there is a significant improvement in sensitivity and detection limits, associated with a more effective production and focalization of SO+ ions. Moreover, by applying the systematics of the IFS with pure O2 injected into the cell (IFS-O2 ) we observed a significant improvement in accuracy and detection limits, making this the method of choice for the quantification of trace sulfur in environmental samples by ICP-MS. CONCLUSIONS: The method described here represents an effective and affordable alternative for the accurate and precise determination of sulfur using single-quadrupole ICP-MS in environmental samples, with LODs and LOQs comparable with those obtained with more expensive instrumentation.

Sustained Elevated Blood Pressure Accelerates Atherosclerosis Development in a Preclinical Model of Disease.

The continuous relationship between blood pressure (BP) and cardiovascular events makes the distinction between elevated BP and hypertension based on arbitrary cut-off values for BP. Even mild BP elevations manifesting as high-normal BP have been associated with cardiovascular risk. We hypothesize that persistent elevated BP increases atherosclerotic plaque development. To evaluate this causal link, we developed a new mouse model of elevated BP based on adeno-associated virus (AAV) gene transfer. We constructed AAV vectors to support transfer of the hRenin and hAngiotensinogen genes. A single injection of AAV-Ren/Ang (1011 total viral particles) induced sustained systolic BP increase (130 ± 20 mmHg, vs. 110 ± 15 mmHg in controls; p = 0.05). In ApoE-/- mice, AAV-induced mild BP elevation caused larger atherosclerotic lesions evaluated by histology (10-fold increase vs. normotensive controls). In this preclinical model, atheroma plaques development was attenuated by BP control with a calcium channel blocker, indicating that a small increase in BP within a physiological range has a substantial impact on plaque development in a preclinical model of atherosclerosis. These data support that non-optimal BP represents a risk for atherosclerosis development. Earlier intervention in elevated BP may prevent or delay morbidity and mortality associated with atherosclerosis.

Optical method to characterize and assess setting evolution of cement pastes: publisher's note.

This publisher's note amends the author affiliations in Appl. Opt.59, D1 (2020)APOPAI0003-693510.1364/AO.59.0000D1.

Optical method to characterize and assess setting evolution of cement pastes.

In this work, a nondestructive and noninvasive technique, based on laser technology and the use of the Kubelka-Munk model to calculate the dynamic behavior of the cement paste from the diffuse reflection properties of both cement components and hydration products, is proposed. Also, the Powers-Brunauer model is used to explain this behavior during the first 9 h of the hydration process. This method allows us to obtain the initial and final cement setting times from the diffuse reflection measurements.

Pharmacological doses of melatonin impede cognitive decline in tau-related Alzheimer models, once tauopathy is initiated, by restoring the autophagic flux.

Alterations in autophagy are increasingly being recognized in the pathogenesis of proteinopathies like Alzheimer's disease (AD). This study was conducted to evaluate whether melatonin treatment could provide beneficial effects in an Alzheimer model related to tauopathy by improving the autophagic flux and, thereby, prevent cognitive decline. The injection of AAV-hTauP301L viral vectors and treatment/injection with okadaic acid were used to achieve mouse and human ex vivo, and in vivo tau-related models. Melatonin (10 µmol/L) impeded oxidative stress, tau hyperphosphorylation, and cell death by restoring autophagy flux in the ex vivo models. In the in vivo studies, intracerebroventricular injection of AAV-hTauP301L increased oxidative stress, neuroinflammation, and tau hyperphosphorylation in the hippocampus 7 days after the injection, without inducing cognitive impairment; however, when animals were maintained for 28 days, cognitive decline was apparent. Interestingly, late melatonin treatment (10 mg/kg), starting once the alterations mentioned above were established (from day 7 to day 28), reduced oxidative stress, neuroinflammation, tau hyperphosphorylation, and caspase-3 activation; these observations correlated with restoration of the autophagy flux and memory improvement. This study highlights the importance of autophagic dysregulation in tauopathy and how administration of pharmacological doses of melatonin, once tauopathy is initiated, can restore the autophagy flux, reduce proteinopathy, and prevent cognitive decline. We therefore propose exogenous melatonin supplementation or the development of melatonin derivatives to improve autophagy flux for the treatment of proteinopathies like AD.

Thyroid Hormone Economy in the Perinatal Mouse Brain: Implications for Cerebral Cortex Development.

Thyroid hormones (THs, T4 and the transcriptionally active hormone T3) play an essential role in neurodevelopment; however, the mechanisms underlying T3 brain delivery during mice fetal development are not well known. This work has explored the sources of brain T3 during mice fetal development using biochemical, anatomical, and molecular approaches. The findings revealed that during late gestation, a large amount of fetal brain T4 is of maternal origin. Also, in the developing mouse brain, fetal T3 content is regulated through the conversion of T4 into T3 by type-2 deiodinase (D2) activity, which is present from earlier prenatal stages. Additionally, D2 activity was found to be essential to mediate expression of T3-dependent genes in the cerebral cortex, and also necessary to generate the transient cerebral cortex hyperthyroidism present in mice lacking the TH transporter Monocarboxylate transporter 8. Notably, the gene encoding for D2 (Dio2) was mainly expressed at the blood-cerebrospinal fluid barrier (BCSFB). Overall, these data signify that T4 deiodinated by D2 may be the only source of T3 during neocortical development. We therefore propose that D2 activity at the BCSFB converts the T4 transported across the choroid plexus into T3, thus supplying the brain with active hormone to maintain TH homeostasis.

Metabolic physiology of the Mayan cichlid fish (Mayaheros uropthalmus): Re-examination of classification as an oxyconformer.

The Mayan cichlid (Mayaheros uropthalmus) is a freshwater fish inhabiting warm, potentially hypoxic and/or brackish waters, in Mexico and Central America. Despite its description as highly hypoxia tolerant, M. uropthalmus has been classified physiologically as an 'oxyconformer', which would place it in a very small (and shrinking) category of fishes that purportedly cannot maintain oxygen consumption (MO2) as ambient PO2 falls. However, hypoxia tolerance is often associated with strong oxyregulation, not oxyconformation as described for M. uropthalmus. To resolve these inconsistencies, we measured MO2, the ambient PO2 at which MO2 begins to decline as PO2 falls (PCrit), and gill ventilation rate (fG) in the Mayan cichlid. Variables were measured at 23o, 28 o and 33 °C and temperature sensitivity (Q10) calculated for each function. MO2 at air saturation was 2.9 ±â€¯0.2, 4.3 ±â€¯0.4, and 5.9 ±â€¯0.3 µmol O2/g/h at 23o, 28o and 33 °C, respectively. PCrits were low at 2.6 ±â€¯0.8 kPa, 3.2 ±â€¯0.8 kPa and 4.7 ±â€¯0.9 kPa at 23o, 28o and 33 °C, respectively. Q10 values for MO2 were 2.56 ±â€¯0.21 (23-28 °C), 1.89 ±â€¯0.15 (28-33 °C) and 2.2 ±â€¯0.1 (full temperature range of 23-33 °C), suggesting overall Q10s typical for tropical freshwater fish. fG was 39 ±â€¯3, 45 ±â€¯4, and 53 ±â€¯6 breaths/min at 23o, 28o and 33 °C, respectively, and increase 2-3 fold in severe hypoxia at each temperature. Experiments employing hyperoxia up to 35 kPa indicate a strong 'hypoxic drive' for gill ventilation. Collectively, these data show that, in contrast to a previous characterization, the Mayan cichlid is a strong oxyregulator exhibiting attributes (e.g. very low PCrit) typical of very hypoxia-tolerant fishes.

Global Transcriptome Analysis of Primary Cerebrocortical Cells: Identification of Genes Regulated by Triiodothyronine in Specific Cell Types.

Thyroid hormones, thyroxine, and triiodothyronine (T3) are crucial for cerebral cortex development acting through regulation of gene expression. To define the transcriptional program under T3 regulation, we have performed RNA-Seq of T3-treated and untreated primary mouse cerebrocortical cells. The expression of 1145 genes or 7.7% of expressed genes was changed upon T3 addition, of which 371 responded to T3 in the presence of cycloheximide indicating direct transcriptional regulation. The results were compared with available transcriptomic datasets of defined cellular types. In this way, we could identify targets of T3 within genes enriched in astrocytes and neurons, in specific layers including the subplate, and in specific neurons such as prepronociceptin, cholecystokinin, or cortistatin neurons. The subplate and the prepronociceptin neurons appear as potentially major targets of T3 action. T3 upregulates mostly genes related to cell membrane events, such as G-protein signaling, neurotransmission, and ion transport and downregulates genes involved in nuclear events associated with the M phase of cell cycle, such as chromosome organization and segregation. Remarkably, the transcriptomic changes induced by T3 sustain the transition from fetal to adult patterns of gene expression. The results allow defining in molecular terms the elusive role of thyroid hormones on neocortical development.

Bloodless reperfusion with the oxygen carrier HBOC-201 in acute myocardial infarction: a novel platform for cardioprotective probes delivery.

Reperfusion, despite being required for myocardial salvage, is associated with additional injury. We hypothesize that infarct size (IS) will be reduced by a period of bloodless reperfusion with hemoglobin-based oxygen carriers (HBOC) before blood-flow restoration. In the pig model, we first characterized the impact of intracoronary perfusion with a fixed volume (600 ml) of a pre-oxygenated acellular HBOC, HBOC-201, on the healthy myocardium. HBOC-201 was administered through the lumen of the angioplasty balloon (i.e., distal to the occlusion site) immediately after onset of coronary occlusion at 1, 0.7, 0.4, or 0.2 ml/kg/min for 12, 17, 30, and 60 min, respectively, followed by blood-flow restoration. Outcome measures were systemic hemodynamics and LV performance assessed by the state-of-the-art cardiac magnetic resonance (CMR) imaging. The best performing HBOC-201 perfusion strategies were then tested for their impact on LV performance during myocardial infarction, in pigs subjected to 45 min mid-left anterior descending (LAD) coronary occlusion. At the end of the ischemia duration, pigs were randomized to regular reperfusion (blood-only reperfusion) vs. bloodless reperfusion (perfusion with pre-oxygenated HBOC-201 distal to the occlusion site), followed by blood-flow restoration. Hemodynamics and CMR-measured LV performance were assessed at 7- and 45-day follow-up. In modifications of the HBOC-201 procedure, glucose and insulin were included to support cardiac metabolism. A total of 66 pigs were included in this study. Twenty healthy pigs (5 per infusion protocol) were used in the study of healthy myocardium. Intracoronary administration of HBOC-201 (600 ml) at varying rates, including a flow of 0.4 ml/kg/min (corresponding to a maximum perfusion time of 30 min), did not damage the healthy myocardium. Slower perfusion (longer infusion time) was associated with permanent LV dysfunction and myocardial necrosis. A total of 46 pigs underwent MI induction. Compared with regular reperfusion, bloodless reperfusion with pre-oxygenated HBOC-201 alone increased IS. This effect was reversed by enrichment of pre-oxygenated HBOC-201 solution with glucose and insulin, resulting in no increase in IS or worsening of long-term ventricular function despite further delaying restoration of blood flow in the LAD. Bloodless reperfusion with a pre-oxygenated HBOC-201 solution supplemented with glucose and insulin is feasible and safe, but did not reduce infarct size. This strategy could be, however, used to deliver agents to the myocardium to treat or prevent ischemia/reperfusion injury before blood-flow restoration.

Toxin Kid uncouples DNA replication and cell division to enforce retention of plasmid R1 in Escherichia coli cells.

Worldwide dissemination of antibiotic resistance in bacteria is facilitated by plasmids that encode postsegregational killing (PSK) systems. These produce a stable toxin (T) and a labile antitoxin (A) conditioning cell survival to plasmid maintenance, because only this ensures neutralization of toxicity. Shortage of antibiotic alternatives and the link of TA pairs to PSK have stimulated the opinion that premature toxin activation could be used to kill these recalcitrant organisms in the clinic. However, validation of TA pairs as therapeutic targets requires unambiguous understanding of their mode of action, consequences for cell viability, and function in plasmids. Conflicting with widespread notions concerning these issues, we had proposed that the TA pair kis-kid (killing suppressor-killing determinant) might function as a plasmid rescue system and not as a PSK system, but this remained to be validated. Here, we aimed to clarify unsettled mechanistic aspects of Kid activation, and of the effects of this for kis-kid-bearing plasmids and their host cells. We confirm that activation of Kid occurs in cells that are about to lose the toxin-encoding plasmid, and we show that this provokes highly selective restriction of protein outputs that inhibits cell division temporarily, avoiding plasmid loss, and stimulates DNA replication, promoting plasmid rescue. Kis and Kid are conserved in plasmids encoding multiple antibiotic resistance genes, including extended spectrum ß-lactamases, for which therapeutic options are scarce, and our findings advise against the activation of this TA pair to fight pathogens carrying these extrachromosomal DNAs.

Evolutionary origin and functional divergence of totipotent cell homeobox genes in eutherian mammals.

BACKGROUND: A central goal of evolutionary biology is to link genomic change to phenotypic evolution. The origin of new transcription factors is a special case of genomic evolution since it brings opportunities for novel regulatory interactions and potentially the emergence of new biological properties. RESULTS: We demonstrate that a group of four homeobox gene families (Argfx, Leutx, Dprx, Tprx), plus a gene newly described here (Pargfx), arose by tandem gene duplication from the retinal-expressed Crx gene, followed by asymmetric sequence evolution. We show these genes arose as part of repeated gene gain and loss events on a dynamic chromosomal region in the stem lineage of placental mammals, on the forerunner of human chromosome 19. The human orthologues of these genes are expressed specifically in early embryo totipotent cells, peaking from 8-cell to morula, prior to cell fate restrictions; cow orthologues have similar expression. To examine biological roles, we used ectopic gene expression in cultured human cells followed by high-throughput RNA-seq and uncovered extensive transcriptional remodelling driven by three of the genes. Comparison to transcriptional profiles of early human embryos suggest roles in activating and repressing a set of developmentally-important genes that spike at 8-cell to morula, rather than a general role in genome activation. CONCLUSIONS: We conclude that a dynamic chromosome region spawned a set of evolutionarily new homeobox genes, the ETCHbox genes, specifically in eutherian mammals. After these genes diverged from the parental Crx gene, we argue they were recruited for roles in the preimplantation embryo including activation of genes at the 8-cell stage and repression after morula. We propose these new homeobox gene roles permitted fine-tuning of cell fate decisions necessary for specification and function of embryonic and extra-embryonic tissues utilised in mammalian development and pregnancy.

Ticks and tick-borne pathogens of dogs along an elevational and land-use gradient in Chiriquí province, Panamá.

Systematic acarological surveys are useful tools in assessing risk to tick-borne infections, especially in areas where consistent clinical surveillance for tick-borne disease is lacking. Our goal was to identify environmental predictors of tick burdens on dogs and tick-borne infectious agents in dog-derived ticks in the Chiriquí Province of western Panama to draw inferences about spatio-temporal variation in human risk to tick-borne diseases. We used a model-selection approach to test the relative importance of elevation, human population size, vegetative cover, and change in landuse on patterns of tick parasitism on dogs. We collected 2074 ticks, representing four species (Rhipicephalus sanguineus, R. microplus, Amblyomma ovale, and Ixodes boliviensis) from 355 dogs. Tick prevalence ranged from 0 to 74% among the sites we sampled, and abundance ranged from 0 to 20.4 ticks per dog with R. sanguineus s.l. being the most commonly detected tick species (97% of all ticks sampled). Whereas elevation was the best single determinant of tick prevalence and abundance on dogs, the top models also included predictor variables describing vegetation cover and landuse change. Specifically, low-elevation areas associated with decreasing vegetative cover were associated with highest tick occurrence on dogs, potentially because of the affinity of R. sanguineus for human dwellings. Although we found low prevalence of tick-borne pathogen genera (two Rickettsia-positive ticks, no R. rickettsia or Ehrlichia spp.) in our study, all of the tick species we collected from dogs are known vectors of zoonotic pathogens. In areas where epidemiological surveillance infrastructure is limited, field-based assessments of acarological risk can be useful and cost-effective tools in efforts to identify high-risk environments for tick-transmitted pathogens.