In the western United States, Lyme disease has been reported primarily from the three Pacific states, especially California, and sporadically or not at all from various mountain states. In California, surveillance for Lyme disease was initiated in 1983, but it was not made a reportable disease in this state until 1989. Nevertheless, approximately 400 human cases were reported by California State Health authorities between 1983 and 1987. In 1982, I began studying the ecology and epidemiology of Lyme disease in the far-western United States in collaboration with Dr. Willy Burgdorfer of the Rocky Mountain Laboratories, Hamilton, Montana, and others. The objectives of this research have been to determine how the Lyme disease spirochete, Borrelia burgdorferi (Bb), is maintained and distributed in natural foci including the routes of transmission to humans and other animals. Five species of ticks have been found infected naturally with Bb or related borreliae during these studies, but of these only the western black-legged tick, lxodes pacificus, has been implicated as a vector to humans. Transovarial and transstadial passage of Bb has been demonstrated in this tick, though the efficiency of these processes for maintenance of the spirochete is still being evaluated. Western fence lizards (Sceloporus occidentalis) and Columbian blacktailed deer (Odocoileus hemionus columbianus) were found to be major hosts of subadult and adult I. pacificus, respectively. Antibodies to Bb, spirochetemias, or both, have been detected in 8 species of wildlife in California (western fence lizard, 2 species of lagomorphs, 2 species of rodents, 3 species of deer). Species exhibiting the highest seropositivity rates (titers ≥1:64) include brush rabbits (≤100%) and black-tailed jackrabbits (≤90%). The widespread distribution of jackrabbits in the West, their prolific breeding habits, infestation by several species of ticks known to harbor Bb, and their high seropositivity rates render them suitable as sentinel animals for surveillance of Lyme disease. The reservoir competencies of some of these species of wildlife including Columbian black-tailed deer, and the vector competencies of their associated ticks, are currently under investigation.

Lyme disease (LD), caused by the spirochete Borrelia burgdorferi (Bb), is the most commonly reported vector-borne disease in the United States. We have been studying the ecology, epidemiology, and prevention of LD since 1982. The primary objectives of this research are intended to clarify the transmission cycles of Bb and closely related spirochetes in diverse habitats; to determine what behaviors and environmental factors elevate the risk of human exposure to Bb-infected ticks; and to evaluate preventive methods. Several genospecies of LD spirochetes are maintained in transmission cycles involving western gray squirrels, dusky-footed wood rats, California kangaroo rats or deer mice, and three species of Ixodes ticks. The western gray squirrel has been implicated as a primary reservoir host of Bb in dense woodlands. The western black-legged tick, Ixodes pacificus, especially the nymphal stage, is the primary bridging vector from wildlife reservoirs to people. In Mendocino County, the prevalence of spirochete-infection in the nymphs typically averages between 5 and 10% (range, <1% to 41% among individual sites) in various subtypes of dense woodlands. Some activities that were found to contribute significantly to risk of exposure to LD or host-seeking I. pacificus ticks included cutting wood, and contact with either low vegetation bordering the uphill margins of hillside-hiking trails or leaf-litter areas and wood in dense woodlands. To determine how people might become infested with I. pacificus nymphs, six behaviors were evaluated as potential risk factors for encountering the nymphs in a hardwood forest. Activities entailing considerable contact with wood (e.g., sitting on logs or against tree trunks) resulted in greater infestation by nymphs than behaviors involving exposure solely to leaf litter. The ultimate goal of this long-term research is to use the basic knowledge gleaned to develop and implement strategies for reducing human exposure to LD and other tick-borne agents.

An increasing number of emerging tick-borne diseases has been reported in the United States since the 1970s. Using metagenomic next generation sequencing, we detected nucleic acid sequences from 2 novel viruses in the family Bunyaviridae and an emerging human rickettsial pathogen, Rickettsia philipii, in a population of the Pacific Coast tick, Dermacentor occidentalis in Mendocino County sampled annually from 2011 to 2014. A total of 250 adults of this human-biting, generalist tick were collected from contiguous chaparral and grassland habitats, and RNA from each individually extracted tick was deep sequenced to an average depth of 7.3 million reads. We detected a Francisella endosymbiont in 174 ticks (70%), and Rickettsia spp. in 19 ticks (8%); Rickettsia-infected ticks contained R. rhipicephali (16 of 250, 6.4%) or R. philipii (3 of 250,1.2%), the agent of eschar-associated febrile illness in humans. The genomes of 2 novel bunyaviruses (>99% complete) in the genera Nairovirus and Phlebovirus were also identified and found to be present in 20-91% of ticks, depending on the year of collection. The high prevalence of these bunyaviruses in sampled Dermacentor ticks suggests that they may be viral endosymbionts, although further studies are needed to determine whether they are infectious for vertebrate hosts, especially humans, and their potential role in tick ecology.

Objective

We determined the potential programming effects of maternal obesity and high-fat (HF) diet during pregnancy and/or lactation on offspring metabolic syndrome.

Study design

A rat model of maternal obesity was created using an HF diet prior to and throughout pregnancy and lactation. At birth, pups were cross-fostered, thereby generating 4 paradigms of maternal diets during pregnancy/lactation: (1) control (Con) diet during pregnancy and lactation (Con/Con), (2) HF during pregnancy and lactation (HF/HF), (3) HF during pregnancy alone (HF/Con), and (4) HF during lactation alone (Con/HF).

Results

Maternal phenotype during pregnancy and the end of lactation evidenced markedly elevated body fat and plasma corticosterone levels in HF dams. In the offspring, the maternal HF diet during pregnancy alone programmed increased offspring adiposity, although with normal body weight, whereas the maternal HF diet during lactation increased both body weight and adiposity. Metabolic disturbances, particularly that of hyperglycemia, were apparent in all groups exposed to the maternal HF diet (during pregnancy and/or lactation), although differences were apparent in the manifestation of insulin resistant vs insulin-deficient phenotypes. Elevated systolic blood pressure was manifest in all groups, implying that exposure to an obese/HF environment is disadvantageous for offspring health, regardless of pregnancy or lactation periods. Nonetheless, the underlying mechanism may differ because offspring that experienced in utero HF exposure had increased corticosterone levels.

Conclusion

Maternal obesity/HF diet has a marked impact on offspring body composition and the risk of metabolic syndrome was dependent on the period of exposure during pregnancy and/or lactation.

BACKGROUND: Fetal exposure to nicotine is not limited to maternal tobacco smoke, as electronic cigarettes have an increased prevalence of use among reproductive aged women. Animal models have shown that nicotine exposure in utero is associated with increased risk of asthma and cognitive deficits, as well as increased expression of the hippocampal glucocorticoid receptor. We hypothesized that in utero nicotine exposure is associated with epigenetic changes in the offspring lung and brain which may contribute to a memory of this exposure METHODS: Sprague-Dawley rat dams received either saline or 2 mg/kg of nicotine by intraperitoneal injection once daily from embryonic day 6 (e6) to e22. Pups were killed on day 1 of life, and brain and lung tissues were harvested (N = 3/ group). RESULTS: We found that nicotine exposed offspring have altered histone modifications in the brain. Dimethylation of lysine 9 of histone H3 is decreased (0.43-fold; p = 0.03) while acetylation is increased (1.79-fold; p = 0.031). Histone deacetylase activity is significantly decreased with nicotine exposure in brain and lung (0.11-fold; p < 0.001; 0.12-fold; p < 0.001, respectively). Expression of splice variant 1.7 of the glucocorticoid receptor is reduced in the nicotine exposed offspring lung (0.25-fold; p = 0.038). CONCLUSION: We conclude that nicotine exposure is associated with epigenetic alterations in the offspring and may lead to susceptibility to adult disease,. Our finding that in utero exposure to nicotine is associated with inhibition of histone deacetylase activity in the brain of offspring is of importance as a similar inhibition has been suggested as a mechanism for the potentiation of addiction.

In the western United States, Ixodes pacificus Cooley & Kohls (Acari: Ixodidae) is the primary vector of the agents causing Lyme disease and granulocytic anaplasmosis in humans. The geographic distribution of the tick is associated with climatic variables that include temperature, precipitation, and humidity, and biotic factors such as the spatial distribution of its primary vertebrate hosts. Here, we explore (1) how climate change may alter the geographic distribution of I. pacificus in California, USA, during the 21^st century, and (2) the spatial overlap among predicted changes in tick habitat suitability, land access, and ownership. Maps of potential future suitability for I. pacificus were generated by applying climate-based species distribution models to a multi-model ensemble of climate change projections for the Representative Concentration Pathway (RCP) 4.5 (moderate emission) and 8.5 (high emission) scenarios for two future periods: mid-century (2026-2045) and end-of-century (2086-2099). Areas climatically-suitable for I. pacificus are projected to expand by 23% (mid-century RCP 4.5) to 86% (end-of-century RCP 8.5) across California, compared to the historical period (1980-2014), with future estimates of total suitable land area ranging from about 88 to 133 thousand km², or up to about a third of California. Regions projected to have the largest area increases in suitability by end-of-century are in northwestern California and the south central and southern coastal ranges. Over a third of the future suitable habitat is on lands currently designated as open access (i.e. publicly available), and by 2100, the amount of these lands that are suitable habitat for I. pacificus is projected to more than double under the most extreme emissions scenario (from ~23,000 to >51,000 km²). Of this area, most is federally-owned (>45,000 km²). By the end of the century, 26% of all federal land in the state is predicted to be suitable habitat for I. pacificus. The resulting maps may facilitate regional planning and preparedness by informing public health and vector control decision-makers.

Abstract Background Small-for-gestational age (SGA) at birth increases risk of development of adult obesity and insulin resistance. A model of SGA rat offspring has been shown to exhibit increased adipose tissue expression of a key adipogenic transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ), and increased fatty acid de novo synthesis during the nursing period, prior to onset of obesity. PPARγ agonists have been studied for potential use in the prevention of insulin resistance. Moreover, SGA adipocytes exhibit age-dependent differences in lipogenesis as mediated by PPARγ. The effects of PPARγ modulators on lipogenic gene expression and de novo lipogenesis on the age-dependent changes in SGA adipocytes are not known. The objectives of this study were: 1) to determine the adipogenic and lipogenic potential in SGA adipocytes at postnatal day 1 (p1) and day 21 (p21), 2) to determine how the PPARγ activator- and repressor-ligands affect the lipogenic potential, and 3) to determine the fatty acid metabolic response to PPARγ activator-ligand treatment. Methods Primary adipocyte cultures from p1 and p21 SGA and Control male offspring were established from a known maternal food-restriction model of SGA. Cell proliferation and Oil Red O (ORO) staining were quantified. Adipocytes were treated with increasing doses of rosiglitazone or bisphenol-A diglycidyl ether (BADGE). PPARγ and SREBP1 protein expression were determined. De novo lipogenesis with rosiglitazone treatment at p21 was studied using 50% U13C-glucose and gas chromatography/mass spectrometry. Results At p1 and p21, SGA demonstrated increased cell proliferation and increased ORO staining. At p21, SGA demonstrated increased lipogenic gene expression and increased glucose-mediated fatty acid de novo synthesis compared with Controls. In response to rosiglitazone, SGA adipocytes further increased glucose utilization for fatty acid synthesis. SGA lipogenic gene expression demonstrated resistance to BADGE treatment. Conclusions SGA adipocytes exhibit an enhanced adipogenic and lipogenic potential in early postnatal life. By p21, SGA demonstrated resistance to PPARγ repressor-ligand treatment, and selective response to high dose PPARγ activator-ligand treatment in adipogenic and lipogenic gene expression. p21 SGA adipocytes revealed increased fatty acid de novo synthesis through a complex relationship with glucose metabolism.