RESUMO
In mammals, environmental cold sensing conducted by peripheral cold thermoreceptor neurons mostly depends on TRPM8, an ion channel that has evolved to become the main molecular cold transducer. This TRP channel is activated by cold, cooling compounds, such as menthol, voltage, and rises in osmolality. TRPM8 function is regulated by kinase activity that phosphorylates the channel under resting conditions. However, which specific residues, how this post-translational modification modulates TRPM8 activity, and its influence on cold sensing are still poorly understood. By mass spectrometry, we identified four serine residues within the N-terminus (S26, S29, S541, and S542) constitutively phosphorylated in the mouse ortholog. TRPM8 function was examined by Ca2+ imaging and patch-clamp recordings, revealing that treatment with staurosporine, a kinase inhibitor, augmented its cold- and menthol-evoked responses. S29A mutation is sufficient to increase TRPM8 activity, suggesting that phosphorylation of this residue is a central molecular determinant of this negative regulation. Biophysical and total internal reflection fluorescence-based analysis revealed a dual mechanism in the potentiated responses of unphosphorylated TRPM8: a shift in the voltage activation curve toward more negative potentials and an increase in the number of active channels at the plasma membrane. Importantly, basal kinase activity negatively modulates TRPM8 function at cold thermoreceptors from male and female mice, an observation accounted for by mathematical modeling. Overall, our findings suggest that cold temperature detection could be rapidly and reversibly fine-tuned by controlling the TRPM8 basal phosphorylation state, a mechanism that acts as a dynamic molecular brake of this thermo-TRP channel function in primary sensory neurons.SIGNIFICANCE STATEMENT Post-translational modifications are one of the main molecular mechanisms involved in adjusting the sensitivity of sensory ion channels to changing environmental conditions. Here we show, for the first time, that constitutive phosphorylation of the well-conserved serine 29 within the N-terminal domain negatively modulates TRPM8 channel activity, reducing its activation by agonists and decreasing the number of active channels at the plasma membrane. Basal phosphorylation of TRPM8 acts as a key regulator of its function as the main cold-transduction channel, significantly contributing to the net response of primary sensory neurons to temperature reductions. This reversible and dynamic modulatory mechanism opens new opportunities to regulate TRPM8 function in pathologic conditions where this thermo-TRP channel plays a critical role.
Assuntos
Membrana Celular/genética , Membrana Celular/metabolismo , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo , Animais , Células COS , Chlorocebus aethiops , Feminino , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/fisiologia , Gânglio Trigeminal/metabolismoRESUMO
Pyramidal neurons in the medial prefrontal cortical layer 2/3 are an essential contributor to the cellular basis of working memory; thus, changes in their intrinsic excitability critically affect medial prefrontal cortex (mPFC) functional properties. Transient Receptor Potential Melastatin 4 (TRPM4), a calcium-activated nonselective cation channel (CAN), regulates the membrane potential in a calcium-dependent manner. In this study, we uncovered the role of TRPM4 in regulating the intrinsic excitability plasticity of pyramidal neurons in the mouse mPFC layer of 2/3 using a combination of conventional and nystatin perforated whole-cell recordings. Interestingly, we found that TRPM4 is open at resting membrane potential, and its inhibition increases input resistance and hyperpolarizes membrane potential. After high-frequency stimulation, pyramidal neurons increase a calcium-activated non-selective cation current, increase the action potential firing, and the amplitude of the afterdepolarization, these effects depend on intracellular calcium. Furthermore, pharmacological inhibition or genetic silencing of TRPM4 reduces the firing rate and the afterdepolarization after high frequency stimulation. Together, these results show that TRPM4 plays a significant role in the excitability of mPFC layer 2/3 pyramidal neurons by modulating neuronal excitability in a calcium-dependent manner.
Assuntos
Córtex Pré-Frontal/metabolismo , Células Piramidais/metabolismo , Canais de Cátion TRPM/metabolismo , Potenciais de Ação/fisiologia , Animais , Cálcio/metabolismo , Masculino , Potenciais da Membrana/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Patch-Clamp , Córtex Pré-Frontal/efeitos dos fármacos , Células Piramidais/efeitos dos fármacos , Células Piramidais/patologia , Canais de Cátion TRPM/fisiologiaRESUMO
An arboreal lifestyle is thought to be central to primate origins, and most extant primate species still live in the trees. Nonetheless, terrestrial locomotion is a widespread adaptation that has arisen repeatedly within the primate lineage. The absence of terrestriality among the New World monkeys (Platyrrhini) is thus notable and raises questions about the ecological pressures that constrain the expansion of platyrrhines into terrestrial niches. Here, we report the results of a natural experiment, comparing patterns of terrestrial behavior in white-faced capuchin monkeys (Cebus capucinus imitator) living on two islands off the Pacific coast of Panama that lack mammalian predators (island sites) with the behavior of capuchins at three sites in central Panama with more intact predator communities (mainland sites). Surveys with camera traps revealed increased terrestriality in island vs. mainland sites. Capuchin detection rates were higher, the range of party sizes observed was larger, and individuals engaged in a wider range of terrestrial behaviors on the islands lacking mammalian predators. Furthermore, females carrying infants were frequently photographed on the ground at the island sites, but never at the mainland sites. These findings support the long-standing hypothesis that predators constrain the exploitation of terrestrial niches by primates. These results are also consistent with the hypothesis that arboreal locomotion imposes costs that primates will avoid by walking on the ground when predation risk is low.
Assuntos
Cebus/fisiologia , Meio Ambiente , Cadeia Alimentar , Locomoção , Animais , Cebus capucinus , Feminino , Ilhas , Masculino , Panamá , Comportamento PredatórioRESUMO
PURPOSE: To report on the outcomes of amniotic membrane transplantation (AMT) for corneal ulceration following infectious keratitis. METHOD: In this retrospective cohort study of 654 patients with culture-proven infectious keratitis from 8 hospitals in Galicia (Spain), a total of 43 eyes of 43 patients (6.6%) underwent AMT for postinfectious corneal ulceration. The indications for AMT were sterile persistent epithelial defects, severe corneal thinning or perforation. RESULTS: AMT was successful in 62.8% of cases, with 37.2% requiring an additional surgery. Median time to healing was 40.0 days (IQR 24.2-101.7 days) and final BCVA was lower than baseline (p = 0.001). Ulcers were large (>3 mm) in 55.8% of cases. Previous herpetic keratitis and topical steroid use were more common in patients who received AMT (p < 0.001). 49 microorganisms (43 bacteria and 6 fungi) were isolated. CONCLUSIONS: AMT is a therapeutic option for complications following infectious keratitis, which present with a sterile persistent epithelial defect, significant corneal thinning or perforation.
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Whether prey species avoid predators and predator species track prey is a poorly understood aspect of predator-prey interactions, given measuring prey tracking by predators and predator avoidance by prey is challenging. A common approach to study these interactions among mammals in field situations is to monitor the spatial proximity of animals at fixed times, using GPS tags fitted to individuals. However, this method is invasive and only allows tracking of a subset of individuals. Here, we use an alternative, noninvasive camera-trapping approach to monitor temporal proximity of predator and prey animals. We deployed camera traps at fixed locations on Barro Colorado Island, Panama, where the ocelot (Leopardus pardalis) is the principal mammalian predator, and tested two hypotheses: (1) prey animals avoid ocelots; and (2) ocelots track prey. We quantified temporal proximity of predators and prey by fitting parametric survival models to the time intervals between subsequent prey and predator captures by camera traps, and then compared the observed intervals to random permutations that retained the spatiotemporal distribution of animal activity. We found that time until a prey animal appeared at a location was significantly longer than expected by chance if an ocelot had passed, and that the time until an ocelot appeared at a location was significantly shorter than expected by chance after prey passage. These findings are indirect evidence for both predator avoidance and prey tracking in this system. Our results show that predator avoidance and prey tracking influence predator and prey distribution over time in a field setting. Moreover, this study demonstrates that camera trapping is a viable and noninvasive alternative to GPS tracking for studying certain predator-prey interactions.
Debido a las dificultades en evaluar como los depredadores rastrean su presa, y como las presas eluden a depredadores, un aspecto todavía poco conocido en la interacción entre depredadores y presas es si estas evitan a depredadores o si estos rastrean las presas. Una enfoque común para estudiar estas interacciones entre mamíferos bajo condiciones de campo es de seguir la proximidad espacial de animales a intervalos fijos, usando marbetes de GPS ajustados a los individuos. Sin embargo, este método es invasivo y solo permite obtener información de un número limitado de individuos. En este estudio, usamos cámaras trampas como método alternativo y no invasivo, para monitorear el proximidad temporal entre depredadores y presas en sitios fijos en Isla Barro Colorado, Panamá, donde los ocelotes (Leopardus pardalis) son el principal mamífero depredador. Evaluamos dos hipótesis: (1) las presas evitan a los ocelotes, y (2) los ocelotes rastrean a las presas. Cuantificamos la proximidad temporal de depredadores y presas ajustando modelos paramétricos de supervivencia a los intervalos de tiempo ocurridos entre observaciones subsecuentes en las cámaras trampas, y luego comparamos los intervalos observados con permutaciones aleatorias que retuvieron la distribución espacio-temporal de la actividad de los animales. Encontramos que, si un ocelote había pasado por dicha área, el tiempo en el cual una presa aparece en una ubicación fue significativamente mayor que lo esperado aleatoriamente. También encontramos que, después de pasar una presa por un área, el tiempo en que un ocelote tarda en aparecer fue significativamente menor que lo esperado al azar. Estos resultados constituyen evidencia indirecta que las presas evitan a los depredadores y que estos rastrean a las presas. Nuestros resultados muestran que la evitación de los depredadores y el rastreo de las presas influyen en la distribución de presas y depredadores a lo largo del tiempo en un escenario natural. Este estudio también demuestra que las cámaras trampas son una alternativa viable y no invasiva, con respecto a marbetes de GPS, para estudiar ciertas interacciones entre presas y depredadores.
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PURPOSE: To evaluate the efficacy of intracameral phenylephrine (IPH) administered as prophylaxis against intraoperative floppy iris syndrome (IFIS) and to analyze the ability of IPH to reverse IFIS. DESIGN: Prospective, multicenter, randomized, comparative case series of fellow eyes. PARTICIPANTS: Forty-two patients receiving tamsulosin who underwent cataract surgery between January and April 2011. METHODS: Phacoemulsification was performed by 2 experienced surgeons at 2 surgical sites (Complexo Hospitalario Universitario Orense and Complexo Hospitalario Universitario A Coruña). One eye of each patient was randomized to receive 0.6 ml of nonpreserved bisulfite-free IPH 1.5% (group 1) or balanced saline solution (group 2) at the start of surgery. If significant miosis or iris prolapse occurred, IPH was injected during phacoemulsification in group 2. No changes were performed in the surgeon's standard fluidic parameters or viscoelastic preferences. Routine topical mydriatics were instilled before surgery. Intraoperative iris billowing and prolapse and pupil size were recorded and videotaped. Surgical complications; adverse events; pre- and postoperative pulse rate and blood pressure; and final best-corrected visual acuity (BCVA), intraocular pressure (IOP), and endothelial cell count (ECC) were recorded. MAIN OUTCOME MEASURES: Incidence of IFIS and change in pupil size after IPH administration in those eyes of group 2 requiring IPH because of significant miosis or iris prolapse. RESULTS: Signs of IFIS were observed in 88.09% of eyes in group 2. No signs of IFS were noted in group 1 (P < 0.001). Significant miosis, iris prolapse, or both occurred in 54.76% of eyes in group 2, although the condition was successfully reverted with IPH, with a significant increase in pupil size after IPH administration (from 4.77±0.88 mm to 6.68±0.93 mm; P=0.000). No intraoperative complications occurred. No significant differences in ECC, BCVA, or IOP were detected between IPH-treated and nontreated eyes. Blood pressure/pulse rate did not differ significantly from preoperative values in IPH-treated cases. CONCLUSIONS: Intracameral phenylephrine is a highly efficient measure for prophylaxis against IFIS. Moreover, the drug can reverse IFIS, restoring iris rigidity and causing the pupil to return to its preoperative size.
Assuntos
Complicações Intraoperatórias/prevenção & controle , Doenças da Íris/prevenção & controle , Hipotonia Muscular/prevenção & controle , Midriáticos/administração & dosagem , Facoemulsificação , Fenilefrina/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Idoso , Pressão Sanguínea/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Doenças da Íris/induzido quimicamente , Masculino , Hipotonia Muscular/induzido quimicamente , Estudos Prospectivos , Pupila/efeitos dos fármacos , Sulfonamidas/efeitos adversos , Síndrome , Tansulosina , Resultado do Tratamento , Acuidade Visual/fisiologiaRESUMO
Epiphytic lifestyles have evolved independently in ecologically, morphologically, and taxonomically diverse plant species. Although this adaptation is widespread among angiosperms, it is only known to have arisen in a single gymnosperm species, Zamia pseudoparasitica (Cycadophyta). Zamia pseudoparasitica is endemic to the mountains of Western Panama, and little is known about the ecology of this unusual cycad. Here, we provide the first report of a potential seed disperser of Z. pseudoparasitica. Between late October 2019 and March 2020, we conducted arboreal camera trapping at three sites along the Talamanca Cordillera in Western Panama, yielding an accumulated survey effort of 271 camera days. Weekly direct observations were also performed using handheld binoculars at one site. Arboreal camera trapping revealed at least seven mammal species that visit this epiphytic cycad. At all three sites, the Northern olingo (Bassaricyon gabbii) was seen visiting individuals of Z. pseudoparasitica repeatedly, both while cones were closed and after they had opened. We estimated the time-varying intensity of the visits throughout our sampling and used mixed models to compare the length of visits when cones were closed versus when they were open. Both duration and time-varying intensity of visits increased after cones had opened and we documented Northern olingo removing and carrying away seeds. We also observed predation by the yellow-eared toucanet (Selenidera spectabilis) which picked and destroyed mature Z. pseudoparasitica seeds. These results suggest that the Northern olingo could be an important seed dispersal agent for this rare epiphytic gymnosperm.
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The Amazon forest has the highest biodiversity on Earth. However, information on Amazonian vertebrate diversity is still deficient and scattered across the published, peer-reviewed, and gray literature and in unpublished raw data. Camera traps are an effective non-invasive method of surveying vertebrates, applicable to different scales of time and space. In this study, we organized and standardized camera trap records from different Amazon regions to compile the most extensive data set of inventories of mammal, bird, and reptile species ever assembled for the area. The complete data set comprises 154,123 records of 317 species (185 birds, 119 mammals, and 13 reptiles) gathered from surveys from the Amazonian portion of eight countries (Brazil, Bolivia, Colombia, Ecuador, French Guiana, Peru, Suriname, and Venezuela). The most frequently recorded species per taxa were: mammals: Cuniculus paca (11,907 records); birds: Pauxi tuberosa (3713 records); and reptiles: Tupinambis teguixin (716 records). The information detailed in this data paper opens up opportunities for new ecological studies at different spatial and temporal scales, allowing for a more accurate evaluation of the effects of habitat loss, fragmentation, climate change, and other human-mediated defaunation processes in one of the most important and threatened tropical environments in the world. The data set is not copyright restricted; please cite this data paper when using its data in publications and we also request that researchers and educators inform us of how they are using these data.
Assuntos
Florestas , Mamíferos , Animais , Biodiversidade , Aves , Brasil , Humanos , Répteis , VertebradosRESUMO
Habitual reliance on tool use is a marked behavioural difference between wild robust (genus Sapajus) and gracile (genus Cebus) capuchin monkeys. Despite being well studied and having a rich repertoire of social and extractive foraging traditions, Cebus sp. rarely use tools and have never been observed using stone tools. By contrast, habitual tool use by Sapajus is widespread. We review theory and discuss factors which might explain these differences in patterns of tool use between Cebus and Sapajus. We then report the first case of habitual stone tool use in a gracile capuchin: a population of white-faced capuchins (Cebus capucinus imitator) in Coiba National Park, Panama who habitually rely on hammerstone and anvil tool use to access structurally protected food items in coastal areas including Terminalia catappa seeds, hermit crabs, marine snails, terrestrial crabs and other items. This behaviour has persisted on one island in Coiba National Park since at least 2004. From 1 year of camera trapping, we found that stone tool use is strongly male-biased. Of the 205 camera trap days where tool use was recorded, adult females were never observed to use stone tools, although they were frequently recorded at the sites and engaged in scrounging behaviour. Stone tool use occurs year-round in this population; over half of all identifiable individuals were observed participating. At the most active tool use site, 83.2% of days where capuchins were sighted corresponded with tool use. Capuchins inhabiting the Coiba archipelago are highly terrestrial, under decreased predation pressure and potentially experience resource limitation compared to mainland populations-three conditions considered important for the evolution of stone tool use. White-faced capuchin tool use in Coiba National Park thus offers unique opportunities to explore the ecological drivers and evolutionary underpinnings of stone tool use in a comparative within- and between-species context.
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PURPOSE: To assess the frequency of pseudoexfoliation syndrome (PXF) in patients scheduled for cataract surgery and to evaluate its association with pupil dilation, lens nucleus hardness, intraocular pressure (IOP), glaucoma, age, and sex. SETTING: Ourense University Hospital, Ourense, Spain. DESIGN: Cross-sectional study. METHODS: This study evaluated eyes scheduled for cataract surgery between January 2013 and July 2013. Pseudoexfoliation was diagnosed in phakic eyes that showed central and/or peripheral white deposits on the lens surface, pupillary margin, or both. Dilated pupils were evaluated with a portable pupil chart. Nucleus hardness was assessed according to the Lens Opacities Classification System III. Diagnosis of glaucoma was based on International Society Geographical and Epidemiological Ophthalmology criteria. RESULTS: Of the 1763 eyes (1093 patients) evaluated, 381 (21.6%) were diagnosed with PXF. The frequency of PXF increased with age from 6.0% in people between 50 year and 60 years to 31.66% in those older than 80 years. In PXF eyes, nuclear cataracts were significantly harder than in non-PXF eyes (P < .001). The mean IOP was significantly higher in PXF eyes than in non-PXF eyes (P = .002). The frequency of glaucoma was higher in PXF eyes (17.4%) than in non-PXF eyes (9.4%), with a statistically significant difference (P < .001). In PXF eyes, the pupil was significantly smaller than in non-PXF eyes (P < .001). CONCLUSIONS: The frequency of PXF was high in the study population and increased with age. Eyes with PXF were associated with significantly harder nuclear cataracts, smaller pupils, and glaucoma. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.
Assuntos
Catarata/complicações , Síndrome de Exfoliação/epidemiologia , Glaucoma de Ângulo Aberto/epidemiologia , Implante de Lente Intraocular , Facoemulsificação , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Síndrome de Exfoliação/diagnóstico , Síndrome de Exfoliação/fisiopatologia , Feminino , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular , Núcleo do Cristalino/patologia , Masculino , Microscopia Acústica , Pessoa de Meia-Idade , Pupila/fisiologia , Fatores Sexuais , Tonometria OcularRESUMO
Rodents are well-known hosts of Trypanosoma cruzi but little is known on the role of some caviomorph rodents. We assessed the occurrence and prevalence of T. cruzi infection in Microcavia australis ("southern mountain, desert or small cavy") and its infectiousness to the vector Triatoma infestans in four rural communities of Tafí del Valle department, northwestern Argentina. Parasite detection was performed by xenodiagnosis and polymerase chain reaction amplification of the hyper-variable region of kinetoplast DNA minicircles of T. cruzi (kDNA-PCR) from blood samples. A total of 51 cavies was captured in traps set up along cavy paths in peridomestic dry-shrub fences located between 25 and 85 m from the nearest domicile. We document the first record of M. australis naturally infected by T. cruzi. Cavies presented a very high prevalence of infection (46.3%; 95% confidence interval, CI=33.0-59.6%). Only one (4%) of 23 cavies negative by xenodiagnosis was found infected by kDNA-PCR. TcI was the only discrete typing unit identified in 12 cavies with a positive xenodiagnosis. The infectiousness to T. infestans of cavies positive by xenodiagnosis or kDNA-PCR was very high (mean, 55.8%; CI=48.4-63.1%) and exceeded 80% in 44% of the hosts. Cavies are highly-competent hosts of T. cruzi in peridomestic habitats near human dwellings in rural communities of Tucumán province in northwestern Argentina.
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Doença de Chagas/veterinária , Doenças dos Roedores/parasitologia , Trypanosoma cruzi/isolamento & purificação , Animais , Argentina/epidemiologia , Doença de Chagas/epidemiologia , Doença de Chagas/parasitologia , Doença de Chagas/transmissão , Estudos Transversais , DNA de Cinetoplasto/genética , Vetores de Doenças , Feminino , Humanos , Masculino , Reação em Cadeia da Polimerase , Prevalência , Doenças dos Roedores/epidemiologia , Doenças dos Roedores/transmissão , Roedores , População Rural , ZoonosesRESUMO
PURPOSE: To evaluate the characteristics of and risk factors for spontaneous late in-the-bag intraocular lens (IOL) dislocation and to analyze the outcomes of surgical correction. SETTING: Department of Ophthalmology, Complejo Hospitalario Orense, Orense, Spain. METHODS: In this retrospective single-surgeon interventional case series, the surgical database of a referral center was searched for cases of late spontaneous in-the-bag IOL dislocation between 2005 and 2009. The main outcome measures were interval between surgery and dislocation, dislocation site and grade, IOL type, associated capsular tension ring (CTR), predisposing factors, surgical technique to correct dislocation, preoperative and postoperative corrected distance visual acuity (CDVA), and surgical complications. RESULTS: Pseudoexfoliation was the main risk factor for in-the-bag IOL dislocation (66.66% of 45 cases identified). A CTR was present in the capsular bag in 8 cases. Dislocation was corrected by repositioning using scleral fixation (20 cases) or iris suturing (1 case), IOL exchange for an anterior chamber IOL (AC IOL) (19 cases) or iris-claw IOL (4 cases), or (3) anterior capsulotomy (1 case). The mean CDVA improved significantly postoperatively (P = .0001); it was 20/40 or better in 28 eyes (62.22%) and 20/25 or better in 10 eyes (22.22%). There was no significant difference in postoperative CDVA between scleral-fixated IOLs and AC IOLs (P = .316). CONCLUSIONS: Pseudoexfoliation was the main risk factor for in-the-bag IOL dislocation. The presence of a CTR in the bag did not prevent dislocation. Satisfactory results were achieved with a low rate of complications using different surgical techniques to correct IOL position. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.