Association of Combined Estrogen-Progestogen and Progestogen-Only Contraceptives with the Development of Cancer.

Combined estrogen-progestogen contraceptives (oral contraceptives or OCs) and progestogen-only contraceptives (POCs) are synthetic steroids that bind to steroid hormone receptors, which are widespread throughout the body. They have a profound effect on cellular physiology. Combined OCs have been classified by the International Agency for Research on Cancer (IARC) as Group 1 carcinogens, but their findings have not been updated recently. In order to update the information and better understand the impact that OCs and POCs have on the risk of development of cancers, a comprehensive literature search was undertaken, focusing on more recently published papers. In agreement with the IARC, the recent literature confirms an increased risk of breast cancer and cervical cancer with the use of OCs. The recent literature also confirms the IARC conclusion that OCs decrease the risk of ovarian and endometrial cancers. However, there is little support from recent studies for the IARC conclusion that OCs decrease the risk of colorectal cancer or increase the risk of liver cancer. For liver cancer, this may be due to the recent studies having been performed in areas where hepatitis is endemic. In one large observational study, POCs also appear to increase the overall risk of developing cancer. OCs and POCs appear to increase the overall risk of cancer when carefully performed studies with the least intrinsic bias are considered. SUMMARY: OCs have been classified as cancer-causing agents, especially leading to increases in breast cancer and cervical cancer. A review of the recent scientific literature was performed to see whether this still appears to be the case. The recent literature supports the cancer-causing role of OCs especially for breast cancer and cervical cancer. Studies also indicate that progesterone-only contraceptives (such as implants and vaginal rings) also can cause cancer. This is especially true for breast cancer and cervical cancer.

A Risk Assessment Model for Bacterial Leaf Spot of Pepper (Capsicum annuum), Caused by Xanthomonas euvesicatoria, Based on Concentrations of Macronutrients, Micronutrients, and Micronutrient Ratios.

The phytopathogenic bacterium Xanthomonas euvesicatoria causes bacterial leaf spot (BLS) of pepper and has a worldwide distribution. BLS is difficult to control and an integrated management strategy that incorporates crop rotation, use of clean seed and clean plants, weed control, resistant varieties, applications of bactericides, biocontrol agents, and systemic acquired resistance (SAR) inducers is generally recommended. However, even with that arsenal of weapons, BLS can still be responsible for severe losses under favorable environmental conditions. Thus, additional tools need to be added to an overall integrated management strategy to combat BLS. In this article, we developed several models from 2012 to 2014 that were based on how macronutrients, micronutrients, and micronutrient ratios affect BLS severity. Factors used to select a model for validation included highly significant P values, high adjusted R2 values, low variance inflation factor values (<5), root mean square error, Mallow's Cp, and high Akaike's information criterion correction values. In addition, salicylic acid (SA) concentrations and relative expression of nonexpresser pathogenesis-related gene1 (NPR1) and pathogenesis-related protein 1 (PR1) in pepper tissues were also considered in model selection. A model (ECGA1) consisting of concentrations of copper, manganese, potassium, and the iron/zinc ratio as independent variables was used for validation in three different commercial pepper fields in Georgia: Colquitt County and Worth County in 2015 and Tift County in 2016. When area under the disease progress curve (AUDPC) values for two field sites (Colquitt and Worth Counties) in 2015 were pulled together and plotted against ECGA1-predicted values for both sites, the resulting relationship was highly significant (P = 0.0001) with an R2 value of 0.92. A significant relationship between observed AUDPC versus predicted values was also observed in Tift County in 2016 (P < 0.001; adjusted R2 = 0.98). Relative gene expression of both NPR1 and PR1 genes was significantly (P < 0.01) higher in pepper grown in predicted low-risk sites compared with pepper from high-risk sites in Colquitt, Worth, and Tift Counties. Although BLS severity will fluctuate depending on environmental conditions, the data indicate that the level of risk at a particular location may be influenced by how macronutrient and micronutrient concentrations affect plant disease resistance genes in the SAR pathway.

Molecular mechanisms for anthelmintic resistance in strongyle nematode parasites of veterinary importance.

Veterinarians rely on a relatively limited spectrum of anthelmintic agents to control nematode parasites in domestic animals. Unfortunately, anthelmintic resistance has been an emerging problem in veterinary medicine. In particular, resistance has emerged among the strongyles, a group of gastrointestinal nematodes that infect a variety of hosts that range from large herbivores to small companion animals. Over the last several decades, a great deal of research effort has been directed toward developing an understanding of the mechanisms conferring resistance against the three major groups of anthelmintics: macrocyclic lactones, benzimidazoles, and nicotinic agonists. Our understanding of anthelmintic resistance has been largely formed by determining the mechanism of action for each drug class and then evaluating drug-resistant nematode isolates for mutations or differences in expression of target genes. More recently, drug efflux pumps have been recognized for their potential contribution to anthelmintic resistance. In this mini-review, we summarize the evidence for mechanisms of resistance in strongyle nematodes.

Media multitasking is associated with distractibility and increased prefrontal activity in adolescents and young adults.

The current generation of young people indulges in more media multitasking behavior (e.g., instant messaging while watching videos) in their everyday lives than older generations. Concerns have been raised about how this might affect their attentional functioning, as previous studies have indicated that extensive media multitasking in everyday life may be associated with decreased attentional control. In the current study, 149 adolescents and young adults (aged 13-24years) performed speech-listening and reading tasks that required maintaining attention in the presence of distractor stimuli in the other modality or dividing attention between two concurrent tasks. Brain activity during task performance was measured using functional magnetic resonance imaging (fMRI). We studied the relationship between self-reported daily media multitasking (MMT), task performance and brain activity during task performance. The results showed that in the presence of distractor stimuli, a higher MMT score was associated with worse performance and increased brain activity in right prefrontal regions. The level of performance during divided attention did not depend on MMT. This suggests that daily media multitasking is associated with behavioral distractibility and increased recruitment of brain areas involved in attentional and inhibitory control, and that media multitasking in everyday life does not translate to performance benefits in multitasking in laboratory settings.

The -521 C/T variant in the dopamine-4-receptor gene (DRD4) is associated with skiing and snowboarding behavior.

Sensation seeking is the tendency to seek out new and thrilling experiences and to take risks for the sake of such experiences. A single-nucleotide polymorphism, -521 C/T (rs1800955) in the promoter region of the dopamine-4-receptor gene (DRD4), is associated with approach-related traits including novelty seeking and extraversion, in some, but not all studies. To our knowledge, no studies have been conducted on the genetics of risk-taking behavior in sports. Using a joint-analysis approach, we measured sensation seeking in two cohorts of experienced male and female skiers and snowboarders (n = 503) using a sports-specific tool developed for this study, the Contextual Sensation Seeking Questionnaire for Skiing and Snowboarding (CSSQ-S), and a more general trait measure, the Zuckerman-Kuhlman Personality Questionnaire impulsive sensation-seeking subscale. We detected, and then replicated a significant association between the DRD4 -521CC genotype and sports-specific sensation seeking as measured using the CSSQ-S (P < 0.001). These data suggest that the DRD4 -521 C/T polymorphism contributes to a "risk-taking phenotype" in skiers and snowboarders, but the variant was not associated with impulsive sensation seeking (P = 0.9).

Perceptions of survivorship care among South Asian female breast cancer survivors.

BACKGROUND AND OBJECTIVES: To explore the perceptions of South Asian (sa) breast cancer survivors concerning their follow-up care, and to determine the optimal content and format of a survivorship care plan (scp) for this population, according to various life stages. METHODS: A survey was mailed to 259 sa women with a diagnosis of nonmetastatic breast cancer who were 18-85 years of age, 3-60 months post-discharge, and not on active treatment. Descriptive statistics and content analysis were applied to the responses. The data were cross-tabulated by age: group A (<44 years), group B (45-54 years), group C (55-64 years), and group D (>64 years). RESULTS: We received 64 completed surveys. The compliance rate for adjuvant hormonal therapy was high (86.3%). Most of the respondents (n = 61, 95.4%) had visited their family doctor within several months (0.5-24 months) after discharge. Their main physical effects concern was fatigue, and anxiety concerning health was the main psychosocial impact. Groups A and B were more concerned about physical appearance, depression, and the impact of cancer on family members. Women in the older groups were concerned about family obligations and work issues. Several women (n = 9, 14.1%) described strain on their marriage and on their relationships with family and friends as significant issues. Slightly more than one third (n = 24, 37.5%) experienced a deepening of faith, and almost as many (n = 23, 35.9%) felt that their illness was something that was meant to happen. CONCLUSIONS: Many of the impacts of breast cancer treatment are shared by women of all ethnic backgrounds. Others-such as high levels of compliance, little reported strain on spousal and family relationships, and the importance of faith-reflect specific cultural variations. These universal and culture-specific themes should all be kept in mind when developing a scp tailored to sa women. The developmental life stage of a woman affects how she views the cancer diagnosis, especially with respect to family, reproduction, and work issues.

Breast cancer survivorship and South Asian women: understanding about the follow-up care plan and perspectives and preferences for information post treatment.

BACKGROUND AND OBJECTIVES: As more treatment options become available and supportive care improves, a larger number of people will survive after treatment for breast cancer. In the present study, we explored the experiences and concerns of female South Asian (sa) breast cancer survivors (bcss) from various age groups after treatment to determine their understanding of follow-up care and to better understand their preferences for a survivorship care plan (scp). METHODS: Patients were identified by name recognition from BC Cancer Agency records for sa patients who were 3-60 months post treatment, had no evidence of recurrence, and had been discharged from the cancer centre to follow-up. Three focus groups and eleven face-to-face semistructured interviews were audio-recorded, transcribed verbatim, cross-checked for accuracy, and analyzed using thematic and content analysis. Participants were asked about their survivorship experiences and their preferences for the content and format of a scp. RESULTS: Fatigue, cognitive changes, fear of recurrence, and depression were the most universal effects after treatment. "Quiet acceptance" was the major theme unique to sa women, with a unique cross-influence between faith and acceptance. Emphasis on a generalized scp with individualized content echoed the wide variation in breast cancer impacts for sa women. Younger women preferred information on depression and peer support. CONCLUSIONS: For sa bcss, many of the psychological and physical impacts of breast cancer diagnosis and treatment may be experienced in common with bcss of other ethnic backgrounds, but the present study also suggests the presence of unique cultural nuances such as spiritual and language-specific support resource needs. The results provide direction for designing key content and format of scps, and information about elements of care that can be customized to individual patient needs.

The Relationship of Food Insecurity to Nutritional Risk in Independent Living Older Adults.

Understanding the factors that augment optimal health during aging is critical as the US older adult population is increasing. Most research about food insecurity, nutritional risk, and perceived health among older adults are in urban areas or congregate living facilities. Thus, the purpose of this project was to study the relationships among these factors, plus activities of daily living, in community-dwelling older adults in a medium-sized city. Using a qualitative-quantitative study design, a cross-sectional survey was completed by 167 low-income senior apartment residents. Food insecurity in this group was higher than the national and state rate, yet nutrition assistance programs were underutilized and participants under 75 years were more food insecure than their older counterparts. Food insecure residents were at greater nutritional risk, had poorer self-reported health status, were more likely to be depressed, and had a less independent function, including limitations on the ability to shop for and prepare food. The study area is desirable to retirees due to lower cost of living; however, access to services, such as grocery stores, public transportation, and health care providers is limited. This research indicates the need for increased outreach, nutrition assistance, and support services to ensure healthy aging in these regions.

Docosahexaenoic acid (DHA) intake estimated from a 7-question survey identifies pregnancies most likely to benefit from high-dose DHA supplementation.

BACKGROUND: Two randomized trials found women with low blood docosahexaenoic acid (DHA; an omega 3 fatty acid) had fewer early preterm births (<34 weeks gestation) if they were assigned to high dose DHA supplementation, however, there is currently no capacity for clinicians who care for pregnancies to obtain a blood assessment of DHA. Determining a way to identify women with low DHA intake whose risk could be lowered by high dose DHA supplementation is desired. OBJECTIVE: To determine if assessing DHA intake can identify pregnancies that benefit from high dose DHA supplementation. STUDY DESIGN: This secondary analysis used birth data from 1310 pregnant women who completed a 7-question food frequency questionnaire (DHA-FFQ) at 16.8 ± 2.5 weeks gestation that is validated to assess DHA status. They were then randomly assigned to a standard (200 mg/day) or high dose (800 or 1000 mg/day) DHA supplement for the remainder of pregnancy. Bayesian logistic regressions were fitted for early preterm birth and preterm birth as a function of DHA intake and assigned DHA dose. RESULTS: Participants who consumed less than 150 mg/day DHA prior to 20 weeks' gestation (n = 810/1310, 58.1%) had a lower Bayesian posterior probability (pp) of early preterm birth if they were assigned to high dose DHA supplementation (1.4% vs 3.9%, pp = 0.99). The effect on preterm birth (<37 weeks) was also significant (11.3% vs 14.8%, pp = 0.97). CONCLUSION: The DHA-FFQ can identify pregnancies that will benefit most from high dose DHA supplementation and reduce the risk of preterm birth. The DHA-FFQ is low burden to providers and patients and could be easily implemented in obstetrical practice.

Early and late preterm birth rates in participants adherent to randomly assigned high dose docosahexaenoic acid (DHA) supplementation in pregnancy.

BACKGROUND: Intention-to-treat analyses do not address adherence. Per protocol analyses treat nonadherence as a protocol deviation and assess if the intervention is effective if followed. OBJECTIVE: To determine the rate of early preterm birth (EPTB, <34 weeks gestation) and preterm birth (PTB, <37 weeks gestation) in participants who adhered to a randomly assigned docosahexaenoic acid (DHA) dose of 1000 mg/day. STUDY DESIGN: Eleven hundred women with a singleton pregnancy were enrolled before 20-weeks' gestation, provided a capsule with 200 mg/day DHA and randomly assigned to two additional capsules containing a placebo or 800 mg of DHA. In the Bayesian Adaptive Design, new randomization schedules were determined at prespecified intervals. In each randomization, the group with the most EPTB was assigned fewer participants than the other group. Adherence was defined a priori as a postpartum red blood cell phospholipid DHA (RBC-PL-DHA) ≥5.5%.and post hoc as ≥8.0% RBC-PL-DHA, the latter after examination of postpartum RBC-PL-DHA. Bayesian mixture models were fitted for gestational age and dichotomized for EPTB and PTB as a function of baseline RBC-PL-DHA and dose-adherence. Bayesian hierarchical models were also fitted for EPTB by dose adherence and quartiles of baseline RBC-PL-DHA. RESULTS: Adherence to the high dose using both RBC-PL-DHA cut points resulted in less EPTB compared to 200 mg [Bayesian posterior probability (pp) = 0.93 and 0.92, respectively]. For participants in the two lowest quartiles of baseline DHA status, adherence to the higher dose resulted in lower EPTB (≥5.5% RBC-PL-DHA, quartiles 1 and 2, pp = 0.95 and 0.96; ≥8% RBC-PL-DHA, quartiles 1 and 2, pp = 0.94 and 0.95). Using the Bayesian model, EPTB was reduced by 65%, from 3.45% to 1.2%, using both cut points. Adherence also reduced PTB before 35, 36 and 37 weeks using both cut points (pp ≥ 0.95). In general, performance of the nonadherent subgroup mirrored that of participants assigned to 200 mg. CONCLUSION: Adherence to high dose DHA reduced EPTB and PTB. The largest effect of adherence on reducing EPTB was observed in women with low baseline DHA levels. CLINICALTRIALS: gov (NCT02626299).

Pinhole micro-SPECT/CT for noninvasive monitoring and quantitation of oncolytic virus dispersion and percent infection in solid tumors.

The purpose of our study was to validate the ability of pinhole micro-single-photon emission computed tomography/computed tomography (SPECT/CT) to: 1) accurately resolve the intratumoral dispersion pattern and 2) quantify the infection percentage in solid tumors of an oncolytic measles virus encoding the human sodium iodide symporter (MV-NIS). Sodium iodide symporter (NIS) RNA level and dispersion pattern were determined in control and MV-NIS-infected BxPC-3 pancreatic tumor cells and mouse xenografts using quantitative, real-time, reverse transcriptase, polymerase chain reaction, autoradiography and immunohistochemistry (IHC). Mice with BxPC-3 xenografts were imaged with (123)I or (99)TcO(4) micro-SPECT/CT. Tumor dimensions and radionuclide localization were determined with imaging software. Linear regression and correlation analyses were performed to determine the relationship between tumor infection percentage and radionuclide uptake (% injected dose per gram) above background and a highly significant correlation was observed (r(2)=0.947). A detection threshold of 1.5-fold above the control tumor uptake (background) yielded a sensitivity of 2.7% MV-NIS-infected tumor cells. We reliably resolved multiple distinct intratumoral zones of infection from non-infected regions. Pinhole micro-SPECT/CT imaging using the NIS reporter demonstrated precise localization and quantitation of oncolytic MV-NIS infection, and can replace more time-consuming and expensive analyses (for example, autoradiography and IHC) that require animal killing.

Utility of a 7- question online screener for DHA intake.

The secondary analyses of two large, recently completed randomized clinical trials of DHA supplementation in pregnancy found that women with a low baseline DHA status benefited from randomization to a higher dose (800 vs 0 and 1000 vs 200 mg/day DHA). To obtain DHA status, it is necessary to obtain a blood sample and conduct an analysis using gas chromatography (GC) or GC-mass spectrometry (GCMS), both barriers to clinics where pregnant women receive advice on nutrition. Participants consuming less than 150 mg/day of DHA at baseline in our recent trial had a lower risk of early preterm birth and preterm birth when assigned to 1000 vs 200 m/day DHA. DHA intake was determined using a 7-question food frequency questionnaire administered by a trained nutritionist. Because the need for trained personnel to administer the questionnaire would be a barrier to implementing this finding in clinical management of pregnancy, the goal of this study was to determine if an online version of the questionnaire could be validly completed without assistance.

Validation of an abbreviated food frequency questionnaire for estimating DHA intake of pregnant women in the United States.

Docosahexaenoic acid (DHA) intake was estimated in pregnant women between 12- and 20-weeks' gestation using the National Cancer Institute's (NCI) Diet History Questionnaire-II (DHQ-II) and a 7-question screener designed to capture DHA intake (DHA Food Frequency Questionnaire, DHA-FFQ). Results from both methods were compared to red blood cell phospholipid DHA (RBC-DHA) weight percent of total fatty acids. DHA intake from the DHA-FFQ was more highly correlated with RBC-DHA (rs=0.528) than the DHQ-II (rs=0.352). Moreover, the DHA-FFQ allowed us to obtain reliable intake data from 1355 of 1400 participants. The DHQ-II provided reliable intake for only 847 of 1400, because many participants only partially completed it and it was not validated for Hispanic participants. Maternal age, parity, and socioeconomic status (SES) were also significant predictors of RBC-DHA. When included with estimated intake from the DHA-FFQ, the model accounted for 36% of the variation in RBC-DHA.

Eco-evolutionary dynamics in Pacific salmon.

Increasing acceptance of the idea that evolution can proceed rapidly has generated considerable interest in understanding the consequences of ongoing evolutionary change for populations, communities and ecosystems. The nascent field of 'eco-evolutionary dynamics' considers these interactions, including reciprocal feedbacks between evolution and ecology. Empirical support for eco-evolutionary dynamics has emerged from several model systems, and we here present some possibilities for diverse and strong effects in Pacific salmon (Oncorhynchus spp.). We specifically focus on the consequences that natural selection on body size can have for salmon population dynamics, community (bear-salmon) interactions and ecosystem process (fluxes of salmon biomass between habitats). For example, we find that shifts in body size because of selection can alter fluxes across habitats by up to 11% compared with ecological (that is, numerical) effects. More generally, we show that selection within a generation can have large effects on ecological dynamics and so should be included within a complete eco-evolutionary framework.

Higher maternal weight is related to poorer fetal autonomic function.

Maternal obesity is an established risk factor for poor infant neurodevelopmental outcomes; however, the link between maternal weight and fetal development in utero is unknown. We investigated whether maternal obesity negatively influences fetal autonomic nervous system (ANS) development. Fetal heart rate variability (HRV) is an index of the ANS that is associated with neurodevelopmental outcomes in the infant. Maternal-fetal magnetocardiograms were recorded using a fetal biomagnetometer at 36 weeks (n = 46). Fetal HRV was represented by the standard deviation of sinus beat-to-beat intervals (SDNN). Maternal weight was measured at enrollment (12-20 weeks) and 36 weeks. The relationships between fetal HRV and maternal weight at both time points were modeled using adjusted ordinary least squares regression models. Higher maternal weight at enrollment and 36 weeks were associated with lower fetal HRV, an indicator of poorer ANS development. Further study is needed to better understand how maternal obesity influences fetal autonomic development and long-term neurodevelopmental outcomes.

Differential Regional Responses in Soluble Monomeric Alpha Synuclein Abundance Following Traumatic Brain Injury.

Alpha synuclein (α-synuclein) is a neuronal protein found predominately in presynaptic terminals. While the pathological effect of α-synuclein aggregates has been a topic of intense study in several neurodegenerative conditions, less attention has been placed on changes in monomeric α-synuclein and related physiological consequences on neuronal function. A growing body of evidence supports an important physiological role of α-synuclein in neurotransmission. In the context of traumatic brain injury (TBI), we hypothesized that the regional abundance of soluble monomeric α-synuclein is altered over a chronic time period post-injury. To this end, we evaluated α-synuclein in the cortex, hippocampus, and striatum of adult rats at 6 h, 1 day, 1, 2, 4, and 8 weeks after controlled cortical impact (CCI) injury. Western blot analysis demonstrated decreased levels of monomer α-synuclein protein in the ipsilateral hippocampus at 6 h, 1 day, 1, 2, and 8 weeks, as well as in the ipsilateral cortex at 1 and 2 weeks and in the ipsilateral striatum at 6 h after CCI compared with sham animals. Immunohistochemical analysis revealed lower α-synuclein and a modest reduction in synaptophysin staining in the ipsilateral hippocampus at 1 week after CCI compared with sham animals, with no evidence of intracellular or extracellular α-synuclein aggregates. Collectively, these findings demonstrate that monomeric α-synuclein protein abundance in the hippocampus is reduced over an extensive (acute-to-chronic) post-injury interval. This deficit may contribute to the chronically impaired neurotransmission known to occur after TBI.

Analgesic effect of magnesium sulfate during total intravenous anesthesia: randomized clinical study.

INTRODUCTION AND OBJECTIVE: Opioids have usually been used as intraoperative analgesic components, regardless of the many adverse effects they are associated with, such as nausea, vomiting, respiratory depression, and hyperalgesia. Several approaches have been investigated to reduce doses used, and magnesium sulfate has been shown to be a valuable analgesic adjunct. The main objective of the present trial was to evaluate the effectiveness of magnesium sulfate as the chief intraoperative analgesic, and the secondary objectives were to assess propofol consumption, postoperative analgesia, and intraoperative hemodynamic stability. METHODS: In this prospective, double-blind trial, 50 patients scheduled to undergo post-bariatric abdominoplasty under general intravenous anesthesia were divided into two groups, to receive remifentanil or magnesium sulfate as intraoperative analgesic. Fentanyl 1 µg kg-1 was the rescue analgesic. RESULTS: Among the patients in the group receiving Magnesium Sulfate (MSG), 64% did not need supplemental analgesia and none of the patients in the Remifentanil Group (RG) required fentanyl. MSG patients showed propofol consumption 36.6% higher (guided by the Bispectral Index - BIS). MSG patients consumed significantly less ephedrine (mean ± SD) than RG patients, respectively 1.52 ± 4.38 mg and 10 ± 10.39 mg, p < 0.001. Mean values of blood concentrations of magnesium were comparable to values previously described in the literature. CONCLUSION: Magnesium sulfate is a safe and effective option for intraoperative analgesia, when avoiding or decreasing opioid use is required.

Recent declines in salmon body size impact ecosystems and fisheries.

Declines in animal body sizes are widely reported and likely impact ecological interactions and ecosystem services. For harvested species subject to multiple stressors, limited understanding of the causes and consequences of size declines impedes prediction, prevention, and mitigation. We highlight widespread declines in Pacific salmon size based on 60 years of measurements from 12.5 million fish across Alaska, the last largely pristine North American salmon-producing region. Declines in salmon size, primarily resulting from shifting age structure, are associated with climate and competition at sea. Compared to salmon maturing before 1990, the reduced size of adult salmon after 2010 has potentially resulted in substantial losses to ecosystems and people; for Chinook salmon we estimated average per-fish reductions in egg production (-16%), nutrient transport (-28%), fisheries value (-21%), and meals for rural people (-26%). Downsizing of organisms is a global concern, and current trends may pose substantial risks for nature and people.

Nerve terminal anchorage protein 1 (TAP-1) is a chondroitin sulfate proteoglycan: biochemical and electron microscopic characterization.

The plasma membranes of the nerve terminal and the postsynaptic cell of electric organ are separated by a basal lamina. We have purified, biochemically characterized, and visualized in the electron microscope a macromolecule which appears to anchor the nerve terminal to this basal lamina. This molecule, terminal anchorage protein 1 (TAP-1) is associated with the nerve terminal membrane of electric organ, has the properties of an integral membrane protein, and is tightly bound to the extracellular matrix (Carlson, S.S., P. Caroni, and R.B. Kelly. 1986. J. Cell Biol. 103:509-520). TAP-1 can be solubilized from an electric organ extracellular matrix preparation with guanidine-HCl/3-[(3-cholamidopropyl)-dimethylammnio]-1-propane sulfonate and purified by a combination of permeation chromatography on Sephacryl S-1000, sedimentation velocity, and ion exchange chromatography on DEAE Sephacel. The total purification from electric organ is 91-fold and results in at least 86% purity. Digestion of the molecule with chondroitin ABC or AC lyase produces a large but similar shift in the molecular weight of the molecule on SDS-PAGE. The presence of chondroitin-4- or 6-sulfate is confirmed by identification of the isolated glycosaminoglycans with cellulose acetate electrophoresis. Gel filtration of the isolated chains indicates an average molecular weight of 42,000. Digestion of TAP-1 with other glycosaminoglycan lyases such as heparitinase indicates that only chondroitin sulfate is present. These results demonstrate that TAP-1 is a proteoglycan. Visualization of TAP-1 in the electron microscope reveals a "bottlebrush" structure expected for a proteoglycan. The molecule has an average total length of 345 +/- 17 nm with 20 +/- 2 side projections of 113 +/- 5 nm in length. These side projections are presumably the glycosaminoglycan side chains. From this structure, we predict that the TAP-1 glycosaminoglycan side chains should have a molecular weight of approximately 50,000, which is in close agreement with the biochemical studies. Both biochemical and morphologic data indicate that TAP-1 has a relative molecular weight of approximately 1.2 X 10(6). The large size of TAP-1 suggests that this molecule could span the synaptic cleft and make a significant contribution to the structure of the nerve terminal basal lamina of electric organ.