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Palmitoleic acid (POA), a nonessential, monounsaturated omega-7 fatty acid (C16:1n7), is a lipid hormone secreted from adipose tissue and has beneficial effects on distant organs, such as the liver and muscle. Interestingly, POA decreases lipogenesis in toxic storage sites such as the liver and muscle, and paradoxically increases lipogenesis in safe storage sites, such as adipose tissue. Furthermore, higher POA levels in humans are correlated with better insulin sensitivity, an improved lipid profile, and a lower incidence of type-2 diabetes and cardiovascular pathologies, such as myocardial infarction. In preclinical animal models, POA improves glucose intolerance, dyslipidemia, and steatosis of the muscle and liver, while improving insulin sensitivity and secretion. This double-blind placebo-controlled clinical trial tests the hypothesis that POA increases insulin sensitivity and decreases hepatic lipogenesis in overweight and obese adult subjects with pre-diabetes. Important to note, that this is the first study ever to use pure (>90%) POA with < 0.3% palmitic acid (PA), which masks the beneficial effects of POA. The possible positive findings may offer a therapeutic and/or preventative pathway against diabetes and related immunometabolic diseases., Competing Interests: MB has a grant funding and a consulting agreement as a scientific advisor role in Tersus Life Sciences, the study sponsor. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cetin, Pedersen, Porter, Adler and Burak.)

Importance: Adolescents and adults report that their sensory integration and processing differences affect their occupational performance and quality of life, thus requiring effective sensory-focused interventions. Researchers have yet to investigate this population's experience of occupational therapy interventions designed to remediate these challenges., Objective: To explore the perceived experience of adolescents and adults with respect to (1) response to intervention, (2) strategies offered to manage sensory differences, and (3) need for services on completion of an intervention., Design: Retrospective, qualitative study., Setting: Zoom or phone call., Participants: Eleven adolescents and adults with sensory integration and processing differences who had previously completed occupational therapy interventions., Intervention: Sensory-based intervention based on the principles of Ayres Sensory Integration® (ASI) and the Sensory Therapies and Research Frame of Reference., Outcomes and Measures: A semistructured interview to obtain data, followed by an in-depth analysis using an inductive coding process to group initial open codes into themes and common subthemes Results: Open codes were grouped into three core themes: (1) therapist-related factors (what the therapist did in treatment); (2) client-related factors (what the client experienced); and (3) follow-up (future needs of the clients). Four main subthemes of the client-therapist relationship emerged: (1) therapeutic alliance; (2) education and knowledge; (3) strategies, tools, and resources; and (4) future needs., Conclusions and Relevance: This study provides a perspective on the experience of adolescents and adults specific to the impact of a sensory-focused occupational therapy intervention on their daily lives. This will help occupational therapists when designing interventions for current and future clients. What This Article Adds: This study highlights the need for further research addressing effective sensory-based interventions for adolescents and adults. It also captures which components of intervention clients deemed helpful and identifies potential targets for future intervention., (Copyright © 2023 by the American Occupational Therapy Association, Inc.)

Cigarette smoking has many serious negative health consequences. The relationship between smoking and SARS-CoV-2 infection is controversial, specifically whether smokers are at increased risk of infection. We investigated the impact of cigarette smoke on ACE2 isoform expression and SARS-CoV-2 infection in differentiated primary human bronchial epithelial cells at the air-liquid-interface (ALI). We assessed the expression of ACE2 in response to CSE and therapeutics reported to modulate ACE2. We exposed ALI cultures to cigarette smoke extract (CSE) and then infected them with SARS-CoV-2. We measured cellular infection using flow cytometry and whole-transwell immunofluorescence. We found that CSE increased expression of full-length ACE2 (flACE2) but did not alter the expression of a Type I-interferon sensitive truncated isoform (dACE2) that lacks the capacity to bind SARS-CoV-2. CSE did not have a significant impact on key mediators of the innate immune response. Importantly, we show that, despite the increase in flACE2, CSE did not alter airway cell infection after CSE exposure. We found that nicotine does not significantly alter flACE2 expression but that NRF2 agonists do lead to an increase in flACE2 expression. This increase was not associated with an increase in SARS-CoV-2 infection. Our results are consistent with the epidemiological data suggesting that current smokers do not have an excess of SARS-CoV-2 infection. but that those with chronic respiratory or cardiovascular disease are more vulnerable to severe COVID-19. They suggest that, in differentiated conducting airway cells, flACE2 expression levels may not limit airway SARS-CoV-2 infection., Competing Interests: The authors declare no conflict of interest., (Crown Copyright © 2023 Published by Elsevier Ltd.)

Importance: Parent training is an essential part of occupational therapy intervention for children with sensory processing and sensory integration (SP-SI) challenges, and parents' learning needs should be considered., Objective: To identify the extent to which adult learning needs are considered in occupational therapy literature addressing parent training as a part of intervention for children with SP-SI challenges., Data Sources: Searches were performed of the following databases: MEDLINE, PsycINFO, CINAHL, Web of Science, EMBASE, and ERIC. The date range was limited to 1990 to 2019 to capture literature focused on family-centered care., Study Selection and Data Collection: Using Arksey and O'Malley's framework for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews Checklist, the following criteria were used to guide the literature searches: population (parents and families of children with SP-SI challenges), intervention (parent training), outcomes (parent learning needs), and concept (parents as adult learners)., Findings: Searches produced 133 peer-reviewed articles, and 5 met the criteria for inclusion. Qualitative thematic analysis, including stakeholder interviews, revealed two themes: (1) Parents focus on children's needs, not their own, and (2) parents benefit from connection with peers and learn through shared experiences., Conclusions and Relevance: Parent training is an essential component of occupational therapy; however, there is limited occupational therapy evidence examining parents' learning needs, specifically parents of children with SP-SI challenges. Future studies should investigate parents' learning needs in relation to occupational therapy intervention for families of children with SP-SI challenges. What This Article Adds: Parents' learning needs are both rarely considered in the occupational therapy literature and important for best practice in pediatric therapy for children with SP-SI challenges. The results of this scoping review point to the need for further investigation of parent training programs specifically examining parents as adult learners., (Copyright © 2023 by the American Occupational Therapy Association, Inc.)

Among mammals, the order Primates is exceptional in having a high taxonomic richness in which the taxa are arboreal, semiterrestrial, or terrestrial. Although habitual terrestriality is pervasive among the apes and African and Asian monkeys (catarrhines), it is largely absent among monkeys of the Americas (platyrrhines), as well as galagos, lemurs, and lorises (strepsirrhines), which are mostly arboreal. Numerous ecological drivers and species-specific factors are suggested to set the conditions for an evolutionary shift from arboreality to terrestriality, and current environmental conditions may provide analogous scenarios to those transitional periods. Therefore, we investigated predominantly arboreal, diurnal primate genera from the Americas and Madagascar that lack fully terrestrial taxa, to determine whether ecological drivers (habitat canopy cover, predation risk, maximum temperature, precipitation, primate species richness, human population density, and distance to roads) or species-specific traits (body mass, group size, and degree of frugivory) associate with increased terrestriality. We collated 150,961 observation hours across 2,227 months from 47 species at 20 sites in Madagascar and 48 sites in the Americas. Multiple factors were associated with ground use in these otherwise arboreal species, including increased temperature, a decrease in canopy cover, a dietary shift away from frugivory, and larger group size. These factors mostly explain intraspecific differences in terrestriality. As humanity modifies habitats and causes climate change, our results suggest that species already inhabiting hot, sparsely canopied sites, and exhibiting more generalized diets, are more likely to shift toward greater ground use.

Background: Quantitative proteomics is able to provide a comprehensive, unbiased description of changes to cells caused by viral infection, but interpretation may be complicated by differential changes in infected and uninfected 'bystander' cells, or the use of non-physiological cellular models. Methods: In this paper, we use fluorescence-activated cell sorting (FACS) and quantitative proteomics to analyse cell-autonomous changes caused by authentic SARS-CoV-2 infection of respiratory epithelial cells, the main target of viral infection in vivo . First, we determine the relative abundance of proteins in primary human airway epithelial cells differentiated at the air-liquid interface (basal, secretory and ciliated cells). Next, we specifically characterise changes caused by SARS-CoV-2 infection of ciliated cells. Finally, we compare temporal proteomic changes in infected and uninfected 'bystander' Calu-3 lung epithelial cells and compare infection with B.29 and B.1.1.7 (Alpha) variants. Results: Amongst 5,709 quantified proteins in primary human airway ciliated cells, the abundance of 226 changed significantly in the presence of SARS-CoV-2 infection (q <0.05 and >1.5-fold). Notably, viral replication proceeded without inducing a type-I interferon response. Amongst 6,996 quantified proteins in Calu-3 cells, the abundance of 645 proteins changed significantly in the presence of SARS-CoV-2 infection (q < 0.05 and > 1.5-fold). In contrast to the primary cell model, a clear type I interferon (IFN) response was observed. Nonetheless, induction of IFN-inducible proteins was markedly attenuated in infected cells, compared with uninfected 'bystander' cells. Infection with B.29 and B.1.1.7 (Alpha) variants gave similar results. Conclusions: Taken together, our data provide a detailed proteomic map of changes in SARS-CoV-2-infected respiratory epithelial cells in two widely used, physiologically relevant models of infection. As well as identifying dysregulated cellular proteins and processes, the effectiveness of strategies employed by SARS-CoV-2 to avoid the type I IFN response is illustrated in both models., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Crozier TWM et al.)

Background: There are limited effective prophylactic/early treatments for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Viral entry requires spike protein binding to the angiotensin-converting enzyme-2 receptor and cleavage by transmembrane serine protease 2 (TMPRSS2), a cell surface serine protease. Targeting of TMPRSS2 by either androgen blockade or direct inhibition is in clinical trials in early SARS-CoV-2 infection., Methods: We used differentiated primary human airway epithelial cells at the air-liquid interface to test the impact of targeting TMPRSS2 on the prevention of SARS-CoV-2 infection., Results: We first modelled the systemic delivery of compounds. Enzalutamide, an oral androgen receptor antagonist, had no impact on SARS-CoV-2 infection. By contrast, camostat mesylate, an orally available serine protease inhibitor, blocked SARS-CoV-2 entry. However, oral camostat is rapidly metabolised in the circulation, with poor airway bioavailability. We therefore modelled local airway administration by applying camostat to the apical surface of differentiated airway cultures. We demonstrated that a brief exposure to topical camostat effectively restricts SARS-CoV-2 infection., Conclusion: These experiments demonstrate a potential therapeutic role for topical camostat for pre- or post-exposure prophylaxis of SARS-CoV-2, which can now be evaluated in a clinical trial., (© 2022 Guo et al.)

Widow spiders are widely known for their potent venom toxins that make them among the few spiders of medical concern. The latrotoxins are the most well-studied widow toxins and include both the vertebrate-specific latrotoxins and the insect-specific latroinsectotoxins (LITs). Previous studies have shown that toxins are not limited to expression in the venom glands of adult spiders; however, gaps exist in latrotoxin screening across all life stages for brown widows, Latrodectus geometricus and southern black widows, Latrodectus mactans. In this study, we screened male and female venom gland, cephalothorax, and abdomen tissues, spiderling cephalothorax and abdomen tissues, and eggs of both L. geometricus and L. mactans, for the presence of three latrotoxins: α-latrotoxin (α-LTX), and α- and δ-latroinsectotoxins (α/δ-LITs). Widows were locally collected. Extracted RNA was used to prepare cDNA that was analyzed by PCR for the presence or absence of latrotoxin expression. Results show that expression profiles between the two species are very similar but not identical. Expression of α-LTX was found in all life stages in all tissues examined for both species. For both species, no LIT expression was detected in eggs and variable patterns of α-LIT expression were detected in spiderlings and adults. Notably, δ-LIT could only be detected in females for both species. Our results show that latrotoxin expression profiles differ within and between widow species. Data on their expression distribution provide further insight into the specific latrotoxins that contribute to toxicity profiles for each life stage in each species and their specific role in widow biology., (© The Author(s) 2021. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: We investigated the diversity of the pygmy marmoset, Cebuella pygmaea, by comparing genetic, morphological and pelage traits of animals from Peru and Ecuador., Materials and Methods: We extracted DNA from museum specimen osteocrusts and from fecal samples collected from free-ranging individuals. We sequenced the mtDNA cytochrome b gene and the control region from samples collected at 13 different sites and used Bayesian inference and Maximum Likelihood to identify distinct clades. We took measurements of the crania of a subset of these specimens (n = 26) and ran a logistic regression to determine if any of the cranial measurements (n = 22) could predict a specimen's clade. In addition, we examined the pelage patterns of the museum specimens and photographs taken of free-ranging individuals and divided them into pelage types based on coloration of the underbelly., Results: We identified two divergent clades, and two distinct groups with clear geographic boundaries within one of those clades. Two measurements of the zygomatic bone perfectly predicted a given individual's mtDNA clade. We found four distinct pelage patterns in our samples, but these patterns are variable within clades and among individuals within the same population., Conclusion: These analyses indicate that the two recognized subspecies of pygmy marmoset should be elevated to the species level (C. pygmaea and C. niveiventris) based on molecular and cranial differences but not on pelage patterns. We provide evidence on the geographic limits of the two clades and identify regions where additional sampling is required to better define the geographic distribution of the two clades., (© 2021 Wiley Periodicals LLC.)

Among non-human primates, alloparental infant care is most extensive in callitrichines, and is thought to be particularly costly for tamarins whose helpers may suffer increased energy expenditure, weight loss, and reduced feeding time and mobility. The costs and benefits of infant care likely vary among group members yet very few wild studies have investigated variable infant care contributions. We studied infant care over an 8-month period in four wild groups of saddleback tamarins in Bolivia to evaluate: (a) what forms of infant care are provided, by whom, and when, (b) how individuals adjust their behavior (activity, vigilance, height) while caring for infants, and (c) whether individuals differ in their infant care contributions. We found that infant carrying, food sharing, and grooming varied among groups, and immigrant males-those who joined the group after infants were conceived-participated less in infant care compared to resident males. Adult tamarins fed less, rested more, and increased vigilance while carrying infants. Although we did not detect changes in overall activity budgets between prepartum and postpartum periods, tamarins spent more time scanning their environments postpartum, potentially reflecting increased predation risk to both carriers and infants during this period. Our study provides the first quantitative data on the timing and amount of infant carrying, grooming, and food transfer contributed by all individuals within and among multiple wild groups, filling a critical knowledge gap about the factors affecting infant care, and highlighting evolutionary hypotheses for cooperative breeding in tamarins., (© 2020 Wiley Periodicals LLC.)

Body mass is a strong predictor of diet and nutritional requirements across a wide range of mammalian taxa. In the case of small-bodied primates, because of their limited gut volume, rapid food passage rate, and high metabolic rate, they are hypothesized to maintain high digestive efficiency by exploiting foods rich in protein, fats, and readily available energy. However, our understanding of the dietary requirements of wild primates is limited because little is known concerning the contributions of their gut microbiome to the breakdown and assimilation of macronutrients and energy. To study how the gut microbiome contributes to the feeding ecology of a small-bodied primate, we analyzed the fecal microbiome composition and metabolome of 22 wild saddleback tamarins (adult body mass 360-390 g) in Northern Bolivia. Samples were analyzed using high-throughput Illumina sequencing of the 16 S rRNA gene V3-V5 regions, coupled with GC-MS metabolomic profiling. Our analysis revealed that the distal microbiome of Leontocebus weddelli is largely dominated by two main bacterial genera: Xylanibacter and Hallella (34.7 ± 14.7 and 22.6 ± 12.4%, respectively). A predictive analysis of functions likely carried out by bacteria in the tamarin gut demonstrated the dominance of membrane transport systems and carbohydrate metabolism as the predominant metabolic pathways. Moreover, given a fecal metabolome composed mainly of glucose, fructose, and lactic acid (21.7 ± 15.9%, 16.5 ± 10.7%, and 6.8 ± 5.5%, respectively), the processing of highly fermentable carbohydrates appears to play a central role in the nutritional ecology of these small-bodied primates. Finally, the results also show a potential influence of environmentally-derived bacteria in colonizing the tamarin gut. These results indicate high energetic turnover in the distal gut of Weddell's saddleback tamarin, likely influenced by dominant bacterial taxa that facilitate dietary dependence on highly digestible carbohydrates present in nectar, plant exudates, and ripe fruits., (© 2019 Wiley Periodicals, Inc.)

Delayed or recurrent coagulopathy can occur up to 14 days after North American rattlesnake envenomation in patients that have been treated with Crotalidae Polyvalent Immune Fab (CroFab). There is little data in the literature characterizing the sequelae of North American rattlesnake envenomation in pregnancy and no previously published reports of recurrent coagulopathy in pregnancy. CASE REPORT: We present 2 cases of first trimester pregnant women requiring readmission and retreatment with Crotalidae Polyvalent Immune Fab (CroFab) after developing recurrent/late coagulopathy following North American Rattlesnake Envenomation. Both patients were initially admitted and treated with CroFab following snakebite and discharged home without coagulopathy. One patient developed significant hypofibrinogenemia and subsequent hemorrhage after spontaneous abortion secondary to recurrent venom induced hypofibrinogenemia. DISCUSSION: Pregnant women with recurrent or late coagulopathy may be at higher risk for hemorrhage and spontaneous abortion and require more frequent laboratory monitoring after initial hospitalization and treatment with antivenom. A lower threshold for re-treatment with CroFab may be warranted in patients with fibrinogen less than 100mg/dL even in the setting of a normal platelet count., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Tin(ii) monosulfide (SnS) is a layered, anisotropic material that is of interest as a two-dimensional semiconductor for opto-electronic, thermoelectric, and piezoelectric applications. In this study, the effect of work function on contact behavior was investigated. Ni/Au, Pd/Au, Cr/Au, and Ti/Au contacts were fabricated onto individual, solution-synthesized, p-type SnS nanoribbons. The lower work function metals (Cr and Ti) formed Schottky contacts, whereas the higher work function metals (Ni and Pd) formed ohmic or semi-ohmic contacts. Of the ohmic contacts, Ni was found to have a lower contact resistance (∼10 -4 Ω cm 2 or lower) than Pd (∼10 -3 Ω cm 2 or lower). Both the calculated Schottky barriers (0.39 and 0.50 eV) for Cr and Ti, respectively, and the ohmic behavior for Ni and Pd agree with behavior predicted by Schottky-Mott theory. The results indicate that high work function metals should be considered to form low resistance contacts to SnS multilayers.

Background: Inflamed environments are typically hypercellular, rich in pro-inflammatory cytokines, and profoundly hypoxic. While the effects of hypoxia on neutrophil longevity and function have been widely studied, little is known about the consequences of this stimulus on eosinophils., Objective: We sought to investigate the effects of hypoxia on several key aspects of eosinophil biology, namely secretion, survival, and their sensitivity to glucocorticosteroids (GCS), agents that normally induce eosinophil apoptosis., Methods: Eosinophils derived from patients with asthma/atopy or healthy controls were incubated under normoxia and hypoxia, with or without glucocorticoids. Activation was measured by flow cytometry, ELISA of cultured supernatants, and F-actin staining; apoptosis and efferocytosis by morphology and flow cytometry; and GCS efficacy by apoptosis assays and qPCR., Results: Hypoxic incubation (3 kPa) caused (i) stabilization of HIF-2α and up-regulation of hypoxia-regulated genes including BNIP3 (BCL2/adenovirus E1B 19-kDa protein-interacting protein 3) and GLUT1 (glucose transporter 1); (ii) secretion of pre-formed IL-8, and Charcot Leyden crystal (CLC) formation, which was most evident in eosinophils derived from atopic and asthmatic donors; (iii) enhanced F-actin formation; (iv) marked prolongation of eosinophil lifespan (via a NF-κB and Class I PI3-kinase-dependent mechanism); and (v) complete abrogation of the normal pro-apoptotic effect of dexamethasone and fluticasone furoate. This latter effect was evident despite preservation of GCS-mediated gene transactivation under hypoxia., Conclusion and Clinical Relevance: These data indicate that hypoxia promotes an eosinophil pro-inflammatory phenotype by enhancing eosinophil secretory function, delaying constitutive apoptosis, and importantly, antagonizing the normal pro-apoptotic effect of GCS. As eosinophils typically accumulate at sites that are relatively hypoxic, particularly during periods of inflammation, these findings may have important implications to understanding the behaviour of these cells in vivo., (© 2016 John Wiley & Sons Ltd.)

Background: Oral baclofen toxicity is extremely rare, but can affect patients with renal disease due to the drug's predominant renal clearance of approximately 69-85%. Patients with severely impaired renal function typically develop symptoms soon after initiating baclofen therapy, even at relatively low doses., Case Report: A 69-year-old woman with a history of hemodialysis-dependent end-stage renal disease presented to the Emergency Department with encephalopathy, ataxia, and dystonia after the addition of a recent baclofen prescription for back pain (10 mg twice daily). She had been taking baclofen as prescribed for approximately 1 week when, the day prior to admission, she had increased her dose to a total of 40 mg. Diagnostic studies demonstrated the patient had chronic, end-stage renal disease and a supratherapeutic concentration of baclofen. Signs and symptoms resolved with hemodialysis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: It is of critical importance for emergency physicians to appreciate impaired baclofen clearance in those with underlying renal disease to obviate the potential for significant drug toxicity., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Protease inhibitors (PIs) are important regulators of physiology and represent anti-parasitic druggable and vaccine targets. We conducted bioinformatic analyses of genome and transcriptome data to determine the protease inhibitor (PI) repertoire in Amblyomma americanum and in 25 other ixodid tick species. For A. americanum, we compared the PI repertoires in fed and unfed, male and female A. americanum ticks. We also analyzed PI repertoires of female 48, 96 and 120 h-fed midgut (MG) and salivary gland (SG) tissues., Results: We found 1,595 putative non-redundant PI sequences across 26 ixodid tick species. Ticks express PIs from at least 18 different families: I1, I2, I4, I8, I21, I25, I29, I31, I32, I35, I39, I43, I51, I53, I63, I68, I72 and I74 (MEROPS). The largest PI families were I2, I4 and I8 and lowest in I21, I31, I32, I35 and I68. The majority (75%) of tick PIs putatively inhibit serine proteases, with ~11 and 9% putatively regulating cysteine or metalloprotease-mediated pathways, respectively, and ~4% putatively regulating multiple/mixed protease types. In A. americanum, we found 370 PIs in female and 354 in male ticks. In A. americanum we found 231 and 442 in unfed and fed ticks, respectively. In females, we found 206 and 164 PIs in SG and MG, respectively. The majority of highly cross-tick species conserved PIs were in families I1, I2, I8, I21, I25, I29, I39 and I43., Conclusions: Ticks appear to express large and diverse repertoires of PIs that primarily target serine protease-mediated pathways. We speculate that PI families with the highest repertoires may contain functionally redundant members while those with the lowest repertoires are functionally non-redundant PIs. We found some highly conserved PIs in the latter category, which we propose as potential candidates for broad-spectrum anti-tick vaccine candidates or druggable targets in tick control.

Since Darwin (), scientists have been puzzled by how behaviors that impose fitness costs on helpers while benefiting their competitors could evolve through natural selection. Hamilton's () theory of inclusive fitness provided an explanation by showing how cooperative behaviors could be adaptive if directed at closely related kin. Recent studies, however, have begun to question whether kin selection is sufficient to explain cooperative behavior in some species (Bergmüller, Johnstone, Russell, & Bshary, ). Many researchers have instead emphasized the importance of direct fitness benefits for helpers in the evolution of cooperative breeding systems. Furthermore, individuals can vary in who, when, and how much they help, and the factors that affect this variation are poorly understood (Cockburn, ; Heinsohn, ). Cooperative breeders thus provide excellent models for the study of evolutionary theories of cooperation and conflict (Cant, )., (© 2017 Wiley Periodicals, Inc.)

Tamarins are reported to live in small multimale-multifemale groups characterized by a single breeding female. Here we present information on the composition and genetic relatedness of individuals in 12 wild-trapped groups of Weddell's saddleback tamarins (Saguinus weddelli) from northern Bolivia to determine if groups are best described as nuclear or extended families suggesting social monogamy or whether groups contain several unrelated same sex adults indicative of social polyandry/polygyny. Mean group size was 6.25 including an average of 2.16 adult males (range 1-4) and 2.08 adult females (1-3). No group contained only one adult male and one adult female and 25% of groups contained two parous females. We estimated the genetic relatedness among individuals using 13 polymorphic microsatellite markers. Across the population, mean relatedness was low and not significantly different among adult males versus among adult females, suggesting that both sexes disperse from their natal groups. Adults of both sexes also tended to have close same-sex adult relatives within their groups; relatedness among adult females of the same group averaged 0.31 and among adult males was 0.26. This suggests that tamarins of one or both sexes sometimes delay dispersal and remain as adults in their natal group or that emigration of same-sexed relatives into the same group may be common. Finally, parentage analyses indicated that, whereas the parents of juveniles generally were present in the group, this was not always the case. Based on these data, published reports of the presence of multiple breeding males and occasionally multiple breeding females in the same group, and the fact that less than 10% of groups in the wild contain a single adult male-adult female pair, we argue that social polyandry best characterizes the composition of tamarin groups and that monogamy is not a common mating pattern in Saguinus weddelli or other tamarin species., (© 2015 Wiley Periodicals, Inc.)

Silencing Amblyomma americanum insulin-like growth factor binding protein-related protein 1 (AamIGFBP-rP1) mRNA prevented ticks from feeding to repletion. In this study, we used recombinant (r)AamIGFBP-rP1 in a series of assays to obtain further insight into the role(s) of this protein in tick feeding regulation. Our results suggest that AamIGFBP-1 is an antigenic protein that is apparently exclusively expressed in salivary glands. We found that both males and females secrete AamIGFBP-rP1 into the host during feeding and confirmed that female ticks secrete this protein from within 24-48 h after attachment. Our data suggest that native AamIGFBP-rP1 is a functional insulin binding protein in that both yeast- and insect cell-expressed rAamIGFBP-rP1 bound insulin, but not insulin-like growth factors. When subjected to anti-blood clotting and platelet aggregation assays, rAamIGFBP-rP1 did not have any effect. Unlike human IGFBP-rP1, which is controlled by trypsinization, rAamIGFBP-rP1 is resistant to digestion, suggesting that the tick protein may not be under mammalian host control at the tick feeding site. The majority of tick-borne pathogens are transmitted 48 h after the tick has attached. Thus, the demonstrated antigenicity and secretion into the host within 24-48 h of the tick starting to feed makes AamIGFBP-rP1 an attractive target for antitick vaccine development., (© 2015 The Royal Entomological Society.)

Ixodes scapularis is arguably the most medically important tick species in the United States. This tick transmits 5 of the 14 human tick-borne disease (TBD) agents in the USA: Borrelia burgdorferi, Anaplasma phagocytophilum, B. miyamotoi, Babesia microti, and Powassan virus disease. Except for the Powassan virus disease, I. scapularis-vectored TBD agents require more than 24h post attachment to be transmitted. This study describes identification of 24h immunogenic I. scapularis tick saliva proteins, which could provide opportunities to develop strategies to stop tick feeding before transmission of the majority of pathogens. A 24h fed female I. scapularis phage display cDNA expression library was biopanned using rabbit antibodies to 24h fed I. scapularis female tick saliva proteins, subjected to next generation sequencing, de novo assembly, and bioinformatic analyses. A total of 182 contigs were assembled, of which ∼19% (35/182) are novel and did not show identity to any known proteins in GenBank. The remaining ∼81% (147/182) of contigs were provisionally identified based on matches in GenBank including ∼18% (27/147) that matched protein sequences previously annotated as hypothetical and putative tick saliva proteins. Others include proteases and protease inhibitors (∼3%, 5/147), transporters and/or ligand binding proteins (∼6%, 9/147), immunogenic tick saliva housekeeping enzyme-like (17%, 25/147), ribosomal protein-like (∼31%, 46/147), and those classified as miscellaneous (∼24%, 35/147). Notable among the miscellaneous class include antimicrobial peptides (microplusin and ricinusin), myosin-like proteins that have been previously found in tick saliva, and heat shock tick saliva protein. Data in this study provides the foundation for in-depth analysis of I. scapularis feeding during the first 24h, before the majority of TBD agents can be transmitted., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Background: Multiple tick saliva proteins, the majority of which are unknown, confer tick resistance in repeatedly infested animals. The objective of this study was to identify the 24-48 h fed Amblyomma americanum tick saliva immuno-proteome. The 24-48 h tick-feeding phase is critical to tick parasitism as it precedes important events in tick biology, blood meal feeding and disease agent transmission. Fed male, 24 and 96 h fed female phage display cDNA expression libraries were biopanned using rabbit antibodies to 24 and 48 h fed A. americanum female tick saliva proteins. Biopanned immuno-cDNA libraries were subjected to next generation sequencing, de novo assembly, and bioinformatic analysis., Results: More than 800 transcripts that code for 24-48 h fed A. americanum immuno-proteins are described. Of the 895 immuno-proteins, 52% (464/895) were provisionally identified based on matches in GenBank. Of these, ~19% (86/464) show high level of identity to other tick hypothetical proteins, and the rest include putative proteases (serine, cysteine, leukotriene A-4 hydrolase, carboxypeptidases, and metalloproteases), protease inhibitors (serine and cysteine protease inhibitors, tick carboxypeptidase inhibitor), and transporters and/or ligand binding proteins (histamine binding/lipocalin, fatty acid binding, calreticulin, hemelipoprotein, IgG binding protein, ferritin, insulin-like growth factor binding proteins, and evasin). Others include enzymes (glutathione transferase, cytochrome oxidase, protein disulfide isomerase), ribosomal proteins, and those of miscellaneous functions (histamine release factor, selenoproteins, tetraspanin, defensin, heat shock proteins)., Conclusions: Data here demonstrate that A. americanum secretes a complex cocktail of immunogenic tick saliva proteins during the first 24-48 h of feeding. Of significance, previously validated immunogenic tick saliva proteins including AV422 protein, calreticulin, histamine release factor, histamine binding/lipocalins, selenoproteins, and paramyosin were identified in this screen, supporting the specificity of the approach in this study. While descriptive, this study opens opportunities for in-depth tick feeding physiology studies.

Recent studies of spatial memory in wild nonhuman primates indicate that foragers may rely on a combination of navigational strategies to locate nearby and distant feeding sites. When traveling in large-scale space, tamarins are reported to encode spatial information in the form of a route-based map. However, little is known concerning how wild tamarins navigate in small-scale space (between feeding sites located at a distance of ≤60 m). Therefore, we collected data on range use, diet, and the angle and distance traveled to visit sequential feeding sites in the same group of habituated Bolivian saddleback tamarins (Saguinus fuscicollis weddelli) in 2009 and 2011. For 7-8 hr a day for 54 observation days, we recorded the location of the study group at 10 min intervals using a GPS unit. We then used GIS software to map and analyze the monkeys' movements and travel paths taken between feeding sites. Our results indicate that in small-scale space the tamarins relied on multiple spatial strategies. In 31% of cases travel was route-based. In the remaining 69% of cases, however, the tamarins appeared to attend to the spatial positions of one or more near-to-site landmarks to relocate feeding sites. In doing so they approached the same feeding site from a mean of 4.5 different directions, frequently utilized different arboreal pathways, and traveled approximately 30% longer than then the straight-line distance. In addition, the monkeys' use of non-direct travel paths allowed them to monitor insect and fruit availability in areas within close proximity of currently used food patches. We conclude that the use of an integrated spatial strategy (route-based travel and attention to near-to-goal landmarks) provides tamarins with the opportunity to relocate productive feeding sites as well as monitor the availability of nearby resources in small-scale space., (© 2013 Wiley Periodicals, Inc.)

Organic anion-transporting polypeptides (Oatps) are an integral part of the detoxification mechanism in vertebrates and invertebrates. These cell surface proteins are involved in mediating the sodium-independent uptake and/or distribution of a broad array of organic amphipathic compounds and xenobiotic drugs. This study describes bioinformatics and biological characterization of 9 Oatp sequences in the Ixodes scapularis genome. These sequences have been annotated on the basis of 12 transmembrane domains, consensus motif D-X-RW-(I,V)-GAWW-X-G-(F,L)-L, and 11 conserved cysteine amino acid residues in the large extracellular loop 5 that characterize the Oatp superfamily. Ixodes scapularis Oatps may regulate non-redundant cross-tick species conserved functions in that they did not cluster as a monolithic group on the phylogeny tree and that they have orthologs in other ticks. Phylogeny clustering patterns also suggest that some tick Oatp sequences transport substrates that are similar to those of body louse, mosquito, eye worm, and filarial worm Oatps. Semi-quantitative RT-PCR analysis demonstrated that all 9 I. scapularis Oatp sequences were expressed during tick feeding. Ixodes scapularis Oatp genes potentially regulate functions during early and/or late-stage tick feeding as revealed by normalized mRNA profiles. Normalized transcript abundance indicates that I. scapularis Oatp genes are strongly expressed in unfed ticks during the first 24h of feeding and/or at the end of the tick feeding process. Except for 2 I. scapularis Oatps, which were expressed in the salivary glands and ovaries, all other genes were expressed in all tested organs, suggesting the significance of I. scapularis Oatps in maintaining tick homeostasis. Different I. scapularis Oatp mRNA expression patterns were detected and discussed with reference to different physiological states of unfed and feeding ticks., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

We designed, synthesized and screened a library of analogs of the organophosphate pesticide metabolite paraoxon against a recombinant variant of human serum paraoxonase-1. Alterations of both the aryloxy leaving group and the retained alkyl chains of paraoxon analogs resulted in substantial changes to binding and hydrolysis, as measured directly by spectrophotometric methods or in competition experiments with paraoxon. Increases or decreases in the steric bulk of the retained groups generally reduced the rate of hydrolysis, while modifications of the leaving group modulated both binding and turnover. Studies on the hydrolysis of phosphoryl azide analogs as well as amino-modified paraoxon analogs, the former being developed as photo-affinity labels, found enhanced tolerance of structural modifications, when compared with O -alkyl substituted molecules. Results from computational modeling predict a predominant active site binding mode for these molecules which is consistent with several proposed catalytic mechanisms in the literature, and from which a molecular-level explanation of the experimental trends is attempted. Overall, the results of this study suggest that while paraoxonase-1 is a promiscuous enzyme, there are substantial constraints in the active site pocket, which may relate to both the leaving group and the retained portion of paraoxon analogs.

Electron channelling contrast imaging of threading dislocations in GaN (0002) substrates and epitaxial films has been demonstrated using a conventional polepiece-mounted backscatter detector in a commercial scanning electron microscope. The influence of accelerating voltage and diffraction vector on contrast features denoting specific threading dislocation types has been studied. As confirmed by coordinated transmission electron microscopy analysis, electron channelling contrast imaging contrast features for edge-type threading dislocations are spatially smaller than mixed-type threading dislocations in GaN. This ability to delineate GaN edge threading dislocations from mixed type was also confirmed by defect-selective etch processing using molten MgO/KOH. This study validates electron channelling contrast imaging as a nondestructive and widely accessible method for spatially mapping and identifying dislocations in GaN with wider applicability for other single-crystal materials., (© 2011 The Authors Journal of Microscopy © 2011 Royal Microscopical Society.)

Charge injection and transport in bottom-contact regioregular-poly(3-hexylthiophene) (rr-P3HT) based field-effect transistors (FETs), wherein the Au source and drain contacts are modified by self-assembled monolayers (SAMs), is reported at different channel length scales. Ultraviolet photoelectron spectroscopy is used to measure the change in metal work function upon treatment with four SAMs consisting of thiol-adsorbates of different chemical composition. Treatment of FETs with electron-poor (electron-rich) SAMs resulted in an increase (decrease) in contact metal work function because of the electron-withdrawing (-donating) tendency of the polar molecules. The change in metal work function affects charge injection and is reflected in the form of the modulation of the contact resistance, R(C). For example, R(C) decreased to 0.18 MΩ in the case of the (electron-poor) 3,5-bis-trifluoromethylbenzenethiol treated contacts from the value of 0.61 MΩ measured in the case of clean Au-contacts, whereas it increased to 0.97 MΩ in the case of the (electron-rich) 3-thiomethylthiophene treated contacts. Field-effect mobility values are observed to be affected in short-channel devices (<20 μm) but not in long-channel devices. This channel-length-dependent behavior of mobility is attributed to grain-boundary limited charge transport at longer channel lengths in these devices.

Callimico goeldii gives birth to single offspring, whereas other callitrichids, including Callithrix jacchus, twin. This study compares maternal effort and infant development in C. goeldii and C. jacchus; it is the first study to look at nursing frequency. Infants were observed from birth for 7 weeks in two captive groups each of C. goeldii and C. jacchus. C. goeldii mothers physiologically invested the same or less than C. jacchus mothers. C. goeldii mothers gained the same amount of weight during pregnancy in absolute terms as did the smaller C. jacchus. This results in a smaller gain in proportion to maternal weight but an equivalent proportional gain on a per fetus basis. C. goeldii mothers nursed their infants less based on duration of nursing bouts compared with C. jacchus mothers. C. goeldii mothers transported their infants exclusively through the first 2 weeks of life, which is longer than C. jacchus mothers, who exclusively transported infants only during the first week of life. As maternal infant carriage declined, other group members transported offspring in both species. C. goeldii infants engaged in independent locomotive sequences later in development and tasted solid foods less frequently than C. jacchus infants when compared at equivalent ages. A single, opportunistic milk sample obtained from a C. goeldii mother when her infant was 48 days old indicates that C. goeldii milk contains gross energy from crude protein within the range of variation observed in Callithrix milk. Despite the similarities in milk quality and prenatal effort in individual fetuses, C. goeldii infants gain weight faster from 0 to 18 months than do C. jacchus infants. A reduction in litter size allows C. goeldii mothers to spend more time carrying their infant and to delay weaning, thereby allowing accelerated infant and juvenile growth rates compared with C. jacchus.

Mycophagy has been documented in a number of species of marmosets and lion tamarins (Callitrichinae) but its effect on ranging behavior is not known. We present the results of 10 years of research on five groups of Goeldi's monkey (Callimico goeldii) at a field site in northwestern Bolivia. We studied the diet and ranging behavior of two of the groups. On average, groups contained 4.5 individuals (range 2.0-9.0), but they gradually decreased in size until only the breeding female remained in the home range. The annual diet was composed of fungi (31.1-34.9%), fruits (34.0-40.6%), prey (17.4-30.1%), and exudates (1.0-10.9%). They had large home ranges (114-150 ha) and over time individuals tended to shift their core areas of use. They used secondary and bamboo forest and forest with dense understories more than expected based on availability. We suggest that the large home ranges and shifting core areas used by C. goeldii are components of a foraging strategy to track patchy, low density, and ephemeral fungal fruiting bodies. Our results, along with data published on other callitrichines, indicate that groups of Leontopithecus, Callithrix, and Callimico that eat fungi have larger home ranges than those that do not. Mycophagy is one of the several factors that evidently affect home range size in callitrichines. Fungi are clearly an important food source for a number of populations, but additional studies are needed to determine why some eat fungi frequently while others do not., ((c) 2010 Wiley-Liss, Inc.)

Fallback foods have been defined as resources for which a species has evolved specific masticatory and digestive adaptations, and are consumed principally when preferred foods are scarce. In the present field investigation, we examine fungi, fruit, and exudate consumption in one group of Callimico goeldii in order to determine the importance of exudates as a fallback food for this species. Based on a total of 1,198 hr of quantitative behavioral data collected between mid-November 2002-August 2003, we found that pod exudates of Parkia velutina accounted for 19% of callimico feeding time in the dry season. This resource was not consumed in the wet season when fruits and fungi were the most common items in the diet. In the dry season of 2005 (July), the same callimico study group did not consume Parkia pod exudates. Instead, the group ate exudates obtained from holes gouged in tree trunks by pygmy marmosets and exudates resulting from natural weathering and insect damage on trunks, roots, and lianas. Pod exudates are reported to contain greater amounts of readily available energy than do trunk and root exudates, and were consumed throughout all periods of the day, particularly in the late afternoon. Trunk and root exudates were consumed principally in the morning. We propose that digestive adaptations of the hindgut, which enable callimicos to exploit fungi (a resource high in structural carbohydrates) year-round, predispose them to efficiently exploit and process exudates as fallback foods when other resources, such as ripe fruits, are scarce., ((c) 2008 Wiley-Liss, Inc.)

The main aim of this investigation was to determine whether a functional relationship existed between epidermal growth factor (EGF) and voltage-gated sodium channel (VGSC) upregulation, both associated with strongly metastatic prostate cancer cells. Incubation with EGF for 24 h more than doubled VGSC current density. Similar treatment with EGF significantly and dose-dependently enhanced the cells' migration through Transwell filters. Both the patch clamp recordings and the migration assay suggested that endogenous EGF played a similar role. Importantly, co-application of EGF and tetrodotoxin, a highly selective VGSC blocker, abolished 65% of the potentiating effect of EGF. It is suggested that a significant portion of the EGF-induced enhancement of migration occurred via VGSC activity., ((c) 2007 Wiley-Liss, Inc.)

We examined the effects of polyspecific associations on the behavior of one group of Callimico goeldii in northwestern Bolivia. Data were collected for 1 year using focal animal sampling at 5-min intervals, for a total of 1,375 observation hours. In total, C. goeldii formed mixed species troops with five groups of Saguinus fuscicollis and six groups of S. labiatus, and these were maintained during 81% of observations. C. goeldii rested more and traveled less while alone than while associated, but neither vigilance behavior in the understory nor habitat use were affected by association status. The composition of the group's diet was different while alone (higher in structural carbohydrates [fungi] and lower in simple sugars [ripe fruits] and protein [insects]) than while associated (fungi 65 vs. 37%; fruits 13 vs. 32%; insects 5 vs. 15%). We propose therefore, that C. goeldii has a lower quality and more narrowly based diet while alone as compared to while associated. The factors that allow for this dietary expansion while in mixed species troops require further investigation., ((c) 2007 Wiley-Liss, Inc.)

Cardiac ATP-sensitive K+ (K(ATP)) channels are formed by Kir6.2 and SUR2A subunits. We produced transgenic mice that express dominant negative Kir6.x pore-forming subunits (Kir6.1-AAA or Kir6.2-AAA) in cardiac myocytes by driving their expression with the alpha-myosin heavy chain promoter. Weight gain and development after birth of these mice were similar to nontransgenic mice, but an increased mortality was noted after the age of 4-5 mo. Transgenic mice lacked cardiac K(ATP) channel activity as assessed with patch clamp techniques. Consistent with a decreased current density observed at positive voltages, the action potential duration was increased in these mice. Some myocytes developed EADs after isoproterenol treatment. Hemodynamic measurements revealed no significant effects on ventricular function (apart from a slightly elevated heart rate), whereas in vivo electrophysiological recordings revealed a prolonged ventricular effective refractory period in transgenic mice. The transgenic mice tolerated stress less well as evident from treadmill stress tests. The proarrhythmogenic features and lack of adaptation to a stress response in transgenic mice suggest that these features are intrinsic to the myocardium and that K(ATP) channels in the myocardium have an important role in protecting the heart from lethal arrhythmias and adaptation to stress situations.

A survey of the distribution and density of Callimico goeldii was conducted at five sites across northwestern Bolivia, in the Department of Pando. C. goeldii was found at two sites north of the Manuripi River, with high densities at one site located along the Acre River. Estimates of habitat availability at these sites suggest that C. goeldii reaches high densities in areas with low human density and well established and extensive bamboo forests. These results, when reviewed with those of prior studies, indicate that the patchy distribution of C. goeldii in Pando is a result of both riverine barriers and the availability of bamboo habitat.

Callimico goeldii, Saguinus fuscicollis, and S. labiatus are sympatric in northern Bolivia and differ from each other in patterns of spatial and structural use of their environment. C. goeldii has a home range five times larger than that of mixed-species troops of S. fuscicollis and S. labiatus. The larger overlapping home range of C. goeldii allows it to move among Saguinus troops, giving it access to a wide range of different microhabitats. All three species use the most common microhabitat in the area, primary forest with dense understory, more than any other microhabitat type. C. goeldii habitat use varies by season, with bamboo and Heliconia microhabitats used more during the dry season. Each species shows preferences for different height classes: C. goeldii is found almost exclusively in the understory, S. fuscicollis uses the understory and middle canopy, and S. labiatus is found mostly in the middle canopy. These height class preferences are reflected in each species' locomotor styles, with C. goeldii showing the highest rates of vertical clinging and leaping, and S. labiatus showing the highest rates of branch-to-branch leaping and quadrupedal movement. The results suggest that C. goeldii may be restricted to forests with dense understory and a mosaic of other microhabitats. Furthermore, C. goeldii does not appear to use its tegulae for large branch foraging, but rather for vertical clinging and leaping between small vertical supports., (Copyright 2003 Wiley-Liss, Inc.)

ATP-sensitive K+ (K(ATP)) channels are abundantly expressed in the heart and may be involved in the pathogenesis of myocardial ischemia. These channels are heteromultimeric, consisting of four pore-forming subunits (Kir6.1, Kir6.2) and four sulfonylurea receptor (SUR) subunits in an octameric assembly. Conventionally, the molecular composition of K(ATP) channels in cardiomyocytes and pancreatic beta -cells is thought to include the Kir6.2 subunit and either the SUR2A or SUR1 subunits, respectively. However, Kir6.1 mRNA is abundantly expressed in the heart, suggesting that Kir6.1 and Kir6.2 subunits may co-assemble to form functional heteromeric channel complexes. Here we provide two independent lines of evidence that heteromultimerization between Kir6.1 and Kir6.2 subunits is possible in the presence of SUR2A. We generated dominant negative Kir6 subunits by mutating the GFG residues in the channel pore to a series of alanine residues. The Kir6.1-AAA pore mutant subunit suppressed both wt-Kir6.1/SUR2A and wt-Kir6.2/SUR2A currents in transfected HEK293 cells. Similarly, the dominant negative action of Kir6.2-AAA does not discriminate between either of the wild-type subunits, suggesting an interaction between Kir6.1 and Kir6.2 subunits within the same channel complex. Biochemical data support this concept: immunoprecipitation with Kir6.1 antibodies also co-precipitates Kir6.2 subunits and conversely, immunoprecipitation with Kir6.2 antibodies co-precipitates Kir6.1 subunits. Collectively, our data provide direct electrophysiological and biochemical evidence for heteromultimeric assembly between Kir6.1 and Kir6.2. This paradigm has profound implications for understanding the properties of native K(ATP)channels in the heart and other tissues., (Copyright 2001 Academic Press.)

Polyspecific associations are an important component of Callimico goeldii behavior and ecology. On average, Callimico goeldii was found in proximity to or in vocal contact with Saguinus troops (S. fuscicollis and S. labiatus) during 53% of all time intervals sampled. Polyspecific associations varied considerably between seasons, however, with association rates peaking during the wet-season month of February (89%) and declining in the dry season, with the lowest rate (13%) in July. The primary benefits of associations appear to be an increased use of the lower and middle canopy, and an increase in feeding behaviors during the wet season. Thus, Callimico goeldii appear to benefit most from associations during the wet season when fruits are its principal food source. Fruits are eaten more in the forest canopy than in the understory; thus, an increase in height use likely permits an increase in the fruit resources on which Callimico goeldii can forage and feed. In addition, Saguinus groups, with their smaller home ranges, are likely to be more knowledgeable than Callimico goeldii about the location and abundance of ripe fruits in their home ranges. Thus, Callimico goeldii may parasitize Saguinus for their fruit knowledge by following them through their ranges. In the dry season, limited dietary overlap between Callimico goeldii and Saguinus groups is likely to make associations less beneficial for Callimico goeldii as they adopt different foraging and ranging strategies., (Copyright 2001 Wiley-Liss, Inc.)

The callitrichines are a specialized radiation of primates that are characterized in part by variable social systems and cooperative infant care. Callimico goeldii, unlike the other callitrichines, have single rather than twin offspring, reducing the need for allocare and permitting synchronous breeding within groups. Low mortality rates among offspring and unstable social groups are suggested to be possible factors that have led to single births among C. goeldii. Single offspring may benefit from greater maternal investment and more frequent food sharing than twin offspring, factors that may help to explain why C. goeldii reaches sexual maturity more rapidly than other callitrichines. In addition, increased breeding opportunities for young C. goeldii females may have selected for rapid maturation rates among this species. Postpartum ovulation and aseasonal resource availability appear to permit females to have biannual birth seasons, further increasing the potential reproductive output., (Copyright 2001 S. Karger AG, Basel)

Introduction: ATP-sensitive K+ channels (K(ATP)) are expressed abundantly in cardiovascular tissues. Blocking this channel in experimental models of ischemia can reduce arrhythmias. We investigated the acute effects of amiodarone on the activity of cardiac sarcolemmal K(ATP) channels and their sensitivity to ATP., Methods and Results: Single K(ATP) channel activity was recorded using inside-out patches from rat ventricular myocytes (symmetric 140 mM K+ solutions and a pipette potential of +40 mV). Amiodarone inhibited K(ATP) channel activity in a concentration-dependent manner. After 60 seconds of exposure to amiodarone, the fraction of mean patch current relative to baseline current was 1.0 +/- 0.05 (n = 4), 0.8 +/- 0.07 (n = 4), 0.6 +/- 0.07 (n = 5), and 0.2 +/- 0.05 (n = 7) with 0, 0.1, 1.0, or 10 microM amiodarone, respectively (IC50 = 2.3 microM). ATP sensitivity was greater in the presence of amiodarone (EC50 = 13 +/- 0.2 microM in the presence of 10 microM amiodarone vs 43 +/- 0.1 microM in controls, n = 5; P < 0.05). Kinetic analysis showed that open and short closed intervals (bursting activity) were unchanged by 1 microM amiodarone, whereas interburst closed intervals were prolonged. Amiodarone also inhibited whole cell K(ATP) channel current (activated by 100 microM bimakalim). After a 10-minute application of amiodarone (10 microM), relative current was 0.71 +/- 0.03 vs 0.92 +/- 0.09 in control (P < 0.03)., Conclusion: Amiodarone rapidly inhibited K(ATP) channel activity by both promoting channel closure and increasing ATP sensitivity. These actions may contribute to the antiarrhythmic properties of amiodarone.