RESUMEN
Introduction: Numerous neurodegenerative diseases are associated with neuronal dysfunction caused by increased redox stress, often linked to aberrant production of redox-active molecules such as nitric oxide (NO) or oxygen free radicals. One such protein affected by redox-mediated changes is the glycolytic enzyme triose-phosphate isomerase (TPI), which has been shown to undergo 3-nitrotyrosination (a NO-mediated post-translational modification) rendering it inactive. The resulting neuronal changes caused by this modification are not well understood. However, associated glycation-induced cytotoxicity has been reported, thus potentially causing neuronal and synaptic dysfunction via compromising synaptic vesicle recycling. Methods: This work uses Drosophila melanogaster to identify the impacts of altered TPI activity on neuronal physiology, linking aberrant TPI function and redox stress to neuronal defects. We used Drosophila mutants expressing a missense allele of the TPI protein, M81T, identified in a previous screen and resulting in an inactive mutant of the TPI protein (TPIM81T , wstd1). We assessed synaptic physiology at the glutamatergic Drosophila neuromuscular junction (NMJ), synapse morphology and behavioural phenotypes, as well as impacts on longevity. Results: Electrophysiological recordings of evoked and spontaneous excitatory junctional currents, alongside high frequency train stimulations and recovery protocols, were applied to investigate synaptic depletion and subsequent recovery. Single synaptic currents were unaltered in the presence of the wstd1 mutation, but frequencies of spontaneous events were reduced. Wstd1 larvae also showed enhanced vesicle depletion rates at higher frequency stimulation, and subsequent recovery times for evoked synaptic responses were prolonged. A computational model showed that TPI mutant larvae exhibited a significant decline in activity-dependent vesicle recycling, which manifests itself as increased recovery times for the readily-releasable vesicle pool. Confocal images of NMJs showed no morphological or developmental differences between wild-type and wstd1 but TPI mutants exhibited learning impairments as assessed by olfactory associative learning assays. Discussion: Our data suggests that the wstd1 phenotype is partially due to altered vesicle dynamics, involving a reduced vesicle pool replenishment, and altered endo/exocytosis processes. This may result in learning and memory impairments and neuronal dysfunction potentially also presenting a contributing factor to other reported neuronal phenotypes.
RESUMEN
Kv3 potassium currents mediate rapid repolarisation of action potentials (APs), supporting fast spikes and high repetition rates. Of the four Kv3 gene family members, Kv3.1 and Kv3.3 are highly expressed in the auditory brainstem and we exploited this to test for subunit-specific roles at the calyx of Held presynaptic terminal in the mouse. Deletion of Kv3.3 (but not Kv3.1) reduced presynaptic Kv3 channel immunolabelling, increased presynaptic AP duration and facilitated excitatory transmitter release; which in turn enhanced short-term depression during high-frequency transmission. The response to sound was delayed in the Kv3.3KO, with higher spontaneous and lower evoked firing, thereby reducing signal-to-noise ratio. Computational modelling showed that the enhanced EPSC and short-term depression in the Kv3.3KO reflected increased vesicle release probability and accelerated activity-dependent vesicle replenishment. We conclude that Kv3.3 mediates fast repolarisation for short precise APs, conserving transmission during sustained high-frequency activity at this glutamatergic excitatory synapse.
Asunto(s)
Sinapsis , Transmisión Sináptica , Potenciales de Acción/fisiología , Animales , Ratones , Neurotransmisores , Terminales Presinápticos/fisiología , Sinapsis/fisiología , Transmisión Sináptica/fisiologíaRESUMEN
The application of deep learning techniques has led to substantial progress in solving a number of critical problems in machine vision, including fundamental problems of scene segmentation and depth estimation. Here, we report a novel deep neural network model, capable of simultaneous scene segmentation and depth estimation from a pair of binocular images. By manipulating the arrangement of binocular image pairs, presenting the model with standard left-right image pairs, identical image pairs or swapped left-right images, we show that performance levels depend on the presence of appropriate binocular image arrangements. Segmentation and depth estimation performance are both impaired when images are swapped. Segmentation performance levels are maintained, however, for identical image pairs, despite the absence of binocular disparity information. Critically, these performance levels exceed those found for an equivalent, monocularly trained, segmentation model. These results provide evidence that binocular image differences support both the direct recovery of depth and segmentation information, and the enhanced learning of monocular segmentation signals. This finding suggests that binocular vision may play an important role in visual development. Better understanding of this role may hold implications for the study and treatment of developmentally acquired perceptual impairments.
Asunto(s)
Aprendizaje Profundo , Visión Binocular , Percepción de Profundidad , Humanos , Disparidad VisualRESUMEN
KEY POINTS: A hallmark trait of ageing skeletal muscle health is a reduction in size and function, which is most pronounced in the fast muscle fibres. We studied older men (74 ± 4 years) with a history of lifelong (>50 years) endurance exercise to examine potential benefits for slow and fast muscle fibre size and contractile function. Lifelong endurance exercisers had slow muscle fibres that were larger, stronger, faster and more powerful than young exercisers (25 ± 1 years) and age-matched non-exercisers (75 ± 2 years). Limited benefits with lifelong endurance exercise were noted in the fast muscle fibres. These findings suggest that additional exercise modalities (e.g. resistance exercise) or other therapeutic interventions are needed to target fast muscle fibres with age. ABSTRACT: We investigated single muscle fibre size and contractile function among three groups of men: lifelong exercisers (LLE) (n = 21, 74 ± 4 years), old healthy non-exercisers (OH) (n = 10, 75 ± 2 years) and young exercisers (YE) (n = 10, 25 ± 1 years). On average, LLE had exercised â¼5 days week-1 for â¼7 h week-1 over the past 53 ± 6 years. LLE were subdivided based on lifelong exercise intensity into performance (LLE-P) (n = 14) and fitness (LLE-F) (n = 7). Muscle biopsies (vastus lateralis) were examined for myosin heavy chain (MHC) slow (MHC I) and fast (MHC IIa) fibre size and function (strength, speed, power). LLE MHC I size (7624 ± 2765 µm2 ) was 25-40% larger (P < 0.001) than YE (6106 ± 1710 µm2 ) and OH (5476 ± 2467 µm2 ). LLE MHC I fibres were â¼20% stronger, â¼10% faster and â¼30% more powerful than YE and OH (P < 0.05). By contrast, LLE MHC IIa size (6466 ± 2659 µm2 ) was similar to OH (6237 ± 2525 µm2 ; P = 0.854), with both groups â¼20% smaller (P < 0.001) than YE (7860 ± 1930 µm2 ). MHC IIa contractile function was variable across groups, with a hierarchical pattern (OH > LLE > YE; P < 0.05) in normalized power among OH (16.7 ± 6.4 W L-1 ), LLE (13.9 ± 4.5 W L-1 ) and YE (12.4 ± 3.5 W L-1 ). The LLE-P and LLE-F had similar single fibre profiles with MHC I power driven by speed (LLE-P) or force (LLE-F), suggesting exercise intensity impacted slow muscle fibre mechanics. These data suggest that lifelong endurance exercise benefited slow muscle fibre size and function. Comparable fast fibre characteristics between LLE and OH, regardless of training intensity, suggest other exercise modes (e.g. resistance training) or myotherapeutics may be necessary to preserve fast muscle fibre size and performance with age.
Asunto(s)
Contracción Muscular , Fibras Musculares Esqueléticas , Anciano , Envejecimiento , Ejercicio Físico , Humanos , Masculino , Músculo Esquelético , Cadenas Pesadas de MiosinaRESUMEN
OBJECTIVE: This study aimed to validate the learning effectiveness of an instructional module in helping first-year dental students and international graduate advanced standing students learn to avoid plagiarism in their scientific writing. METHOD: The module was administered to a total of 226 first year dental students (157 at the University of Pittsburgh, in 2018 and 2019; 69 at the University of Illinois at Chicago, in 2019), and a total of 102 international graduate advanced standing students at the University of Illinois at Chicago, in 2019 and 2020. Psychometric analysis of the module's test items confirmed reliability and validity. RESULTS: An independent sample t-test performed on the module pretest scores determined that the first -year dental students entered their programs with more knowledge about plagiarism than the international graduate advanced standing students. Mean differences were calculated between pretest and posttest scores for each group and indicated that the module was equally effective at helping both groups learn to avoid plagiarism. An independent sample t-test compared the posttest mean scores of the 2 groups and determined that the first -year students achieved a greater learning outcome from the module. An independent sample t-test for Equality of Means with Levene's Test for Equality of Variances were performed to compare the mean differences between posttest and pretest scores for the 2 groups. These tests indicated that the 2 groups learned to avoid plagiarism at the same rate. CONCLUSIONS: The instructional module proved to be valid, reliable, effective, and time-efficient in improving student knowledge about avoiding plagiarism.
Asunto(s)
Plagio , Estudiantes de Odontología , Chicago , Humanos , Aprendizaje , Reproducibilidad de los ResultadosRESUMEN
We examined the influence of lifelong aerobic exercise on skeletal muscle size, function, and adiposity. Young exercisers [YE; n = 20, 10 women (W), 25 ± 1 yr], lifelong exercisers (LLE; n = 28, 7 W, 74 ± 2 yr), and old healthy nonexercisers (OH; n = 20, 10 W, 75 ± 1 yr) were studied. On average, LLE exercised 5 days/wk for 7 h/wk over the past 52 ± 1 yr. The LLE men were subdivided by exercise intensity [Performance (LLE-P), n = 14; Fitness (LLE-F), n = 7]. Upper and lower leg muscle size and adiposity [intermuscular adipose tissue (IMAT)] were determined via MRI, and quadriceps isotonic and isometric function was assessed. For the quadriceps, aging decreased muscle size, isotonic and isometric strength, contraction velocity (men only), and power (P < 0.05). In women, LLE did not influence muscle size or function. In men, LLE attenuated the decline in muscle size and isometric strength by ~50% (P < 0.05). LLE did not influence other aspects of muscle function, nor did training intensity influence muscle size or function. For the triceps surae, aging decreased muscle size only in the women, whereas LLE (both sexes) and training intensity (LLE men) did not influence muscle size. In both sexes, aging increased thigh and calf IMAT by ~130% (P < 0.05), whereas LLE attenuated the thigh increase by ~50% (P < 0.05). In the LLE men, higher training intensity decreased thigh and calf IMAT by ~30% (P < 0.05). In summary, aging and lifelong aerobic exercise influenced muscle size, function, and adipose tissue infiltration in a sex- and muscle-specific fashion. Higher training intensity throughout the life span provided greater protection against adipose tissue infiltration into muscle.NEW & NOTEWORTHY This is the first study to examine skeletal muscle size, function, and adiposity in women and men in their eighth decade of life that have engaged in lifelong aerobic exercise. The findings reveal sex and upper and lower leg muscle group-specific benefits related to skeletal muscle size, function, and adiposity and that exercise intensity influences intermuscular adiposity. This emerging cohort will further our understanding of the health implications of maintaining exercise throughout the life span.
Asunto(s)
Adiposidad , Ejercicio Físico , Músculo Esquelético/fisiología , Tejido Adiposo , Adulto , Anciano , Envejecimiento , Femenino , Humanos , Extremidad Inferior/fisiología , Masculino , Fuerza Muscular , Adulto JovenRESUMEN
The purpose of this study was to examine the effects of lifelong aerobic exercise on single-muscle fiber performance in trained women (LLE; n = 7, 72 ± 2 yr) by comparing them to old healthy nonexercisers (OH; n = 10, 75 ± 1 yr) and young exercisers (YE; n = 10, 25 ± 1 yr). On average, LLE had exercised ~5 days/wk for ~7 h/wk over the past 48 ± 2 yr. Each subject had a vastus lateralis muscle biopsy to examine myosin heavy chain (MHC) I and IIa single-muscle fiber size and function (strength, speed, power). MHC I fiber size was similar across all three cohorts (YE = 5,178 ± 157, LLE = 4,983 ± 184, OH = 4,902 ± 159 µm2). MHC IIa fiber size decreased (P < 0.05) 36% with aging (YE = 4,719 ± 164 vs. OH = 3,031 ± 153 µm2), with LLE showing a similar 31% reduction (3,253 ± 189 µm2). LLE had 17% more powerful (P < 0.05) MHC I fibers and offset the 18% decline in MHC IIa fiber power observed with aging (P < 0.05). The LLE contractile power was driven by greater strength (+11%, P = 0.056) in MHC I fibers and elevated contractile speed (+12%, P < 0.05) in MHC IIa fibers. These data indicate that lifelong exercise did not benefit MHC I or IIa muscle fiber size. However, LLE had contractile function adaptations that enhanced MHC I fiber power and preserved MHC IIa fiber power through different contractile mechanisms (strength vs. speed). The single-muscle fiber contractile properties observed with lifelong aerobic exercise are unique and provide new insights into aging skeletal muscle plasticity in women at the myocellular level.NEW & NOTEWORTHY This is the first investigation to examine the effects of lifelong exercise on single-muscle fiber physiology in women. Nearly 50 yr of moderate to vigorous aerobic exercise training resulted in enhanced slow-twitch fiber power primarily by increasing force production, whereas fast-twitch fiber power was preserved primarily by increasing contractile speed. These unique muscle fiber power profiles helped offset the effects of fast-twitch fiber atrophy and highlight the benefits of lifelong aerobic exercise for myocellular health.
Asunto(s)
Longevidad/fisiología , Fibras Musculares de Contracción Rápida/fisiología , Fibras Musculares de Contracción Lenta/fisiología , Cadenas Pesadas de Miosina/fisiología , Acondicionamiento Físico Humano/fisiología , Adulto , Anciano , Femenino , Humanos , Técnicas In Vitro , Adulto JovenRESUMEN
Primates are facing an impending extinction crisis, driven by extensive habitat loss, land use change and hunting. Climate change is an additional threat, which alone or in combination with other drivers, may severely impact those taxa unable to track suitable environmental conditions. Here, we investigate the extent of climate and land use/cover (LUC) change-related risks for primates. We employed an analytical approach to objectively select a subset of climate scenarios, for which we then calculated changes in climatic and LUC conditions for 2050 across primate ranges (N = 426 species) under a best-case scenario and a worst-case scenario. Generalized linear models were used to examine whether these changes varied according to region, conservation status, range extent and dominant habitat. Finally, we reclassified primate ranges based on different magnitudes of maximum temperature change, and quantified the proportion of ranges overall and of primate hotspots in particular that are likely to be exposed to extreme temperature increases. We found that, under the worst-case scenario, 74% of Neotropical forest-dwelling primates are likely to be exposed to maximum temperature increases up to 7°C. In contrast, 38% of Malagasy savanna primates will experience less pronounced warming of up to 3.5°C. About one quarter of Asian and African primates will face up to 50% crop expansion within their range. Primary land (undisturbed habitat) is expected to disappear across species' ranges, whereas secondary land (disturbed habitat) will increase by up to 98%. With 86% of primate ranges likely to be exposed to maximum temperature increases >3°C, primate hotspots in the Neotropics are expected to be particularly vulnerable. Our study highlights the fundamental exposure risk of a large percentage of primate ranges to predicted climate and LUC changes. Importantly, our findings underscore the urgency with which climate change mitigation measures need to be implemented to avert primate extinctions on an unprecedented scale.
Asunto(s)
Cambio Climático , Conservación de los Recursos Naturales , Animales , Ecosistema , Primates , Medición de RiesgoRESUMEN
Responses of microbial communities to nanotoxicity in aquatic ecosystems are largely unknown, particularly with respect to relationship between community dynamics and functions. Here, periphytic biofilms were selected as a model of species-rich microbial communities to elucidate their responses when exposed to titanium dioxide nanoparticles (TiO2-NPs). Especially, the relationships between the functions (e.g. organic matter and Cu2+ removal) and community dynamics after long-term exposure to TiO2-NPs were assessed systematically. After 5days exposure to TiO2-NPs (5mgL-1), periphytic biofilms showed sustainable functions in pollutant removal and strong plasticity in defensing the toxic disturbance of TiO2-NPs, including photosynthesis and carbon metabolic diversity. The sustainable pollutant removal functions of periphytic biofilms were attributed to their functional redundancy. Specifically, periphytic biofilms altered their composition with cyanobacteria, Sphingobacteriia and Spirochaetes being the newly dominant taxa, and changed the carbon substrate utilization pattern to maintain high photosynthesis and metabolic rates. Moreover, extracellular polymeric substances (EPS) especially proteins were overproduced to bind the NPs and thereby reduce the nanotoxicity. The information obtained in this study may greatly help to understand the interactions between microbial community dynamics and function under NPs exposure conditions and functional redundancy is an important mechanism of periphytic biofilms to maintain sustainable functions.
Asunto(s)
Biopelículas/efectos de los fármacos , Cobre/metabolismo , Nanopartículas/toxicidad , Titanio/toxicidad , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/toxicidad , Bacillus/efectos de los fármacos , Bacillus/fisiología , Biopelículas/crecimiento & desarrollo , Chlorophyta/efectos de los fármacos , Chlorophyta/fisiología , Diatomeas/efectos de los fármacos , Diatomeas/fisiología , Microalgas/efectos de los fármacos , Microalgas/fisiología , Microcystis/efectos de los fármacos , Microcystis/fisiología , Nostoc/efectos de los fármacos , Nostoc/fisiología , Fotosíntesis/efectos de los fármacos , Aguas ResidualesRESUMEN
The purpose of this study was to examine the effects of aerobic lifelong exercise (LLE) on maximum oxygen consumption (VÌo2max) and skeletal muscle metabolic fitness in trained women ( n = 7, 72 ± 2 yr) and men ( n = 21, 74 ± 1 yr) and compare them to old, healthy nonexercisers (OH; women: n = 10, 75 ± 1 yr; men: n = 10, 75 ± 1 yr) and young exercisers (YE; women: n = 10, 25 ± 1 yr; men: n = 10, 25 ± 1 yr). LLE men were further subdivided based on intensity of lifelong exercise and competitive status into performance (LLE-P, n = 14) and fitness (LLE-F, n = 7). On average, LLE exercised 5 day/wk for 7 h/wk over the past 52 ± 1 yr. Each subject performed a maximal cycle test to assess VÌo2max and had a vastus lateralis muscle biopsy to examine capillarization and metabolic enzymes [citrate synthase, ß-hydroxyacyl-CoA dehydrogenase (ß-HAD), and glycogen phosphorylase]. VÌo2max had a hierarchical pattern (YE > LLE > OH, P < 0.05) for women (44 ± 2 > 26 ± 2 > 18 ± 1 ml·kg-1·min-1) and men (53 ± 3 > 34 ± 1 > 22 ± 1 ml·kg-1·min-1) and was greater ( P < 0.05) in LLE-P (38 ± 1 ml·kg-1·min-1) than LLE-F (27 ± 2 ml·kg-1·min-1). LLE men regardless of intensity and women had similar capillarization and aerobic enzyme activity (citrate synthase and ß-HAD) as YE, which were 20%-90% greater ( P < 0.05) than OH. In summary, these data show a substantial VÌo2max benefit with LLE that tracked similarly between the sexes, with further enhancement in performance-trained men. For skeletal muscle, 50+ years of aerobic exercise fully preserved capillarization and aerobic enzymes, regardless of intensity. These data suggest that skeletal muscle metabolic fitness may be easier to maintain with lifelong aerobic exercise than more central aspects of the cardiovascular system. NEW & NOTEWORTHY Lifelong exercise (LLE) is a relatively new and evolving area of study with information especially limited in women and individuals with varying exercise intensity habits. These data show a substantial maximal oxygen consumption benefit with LLE that tracked similarly between the sexes. Our findings contribute to the very limited skeletal muscle biopsy data from LLE women (>70 yr), and similar to men, revealed a preserved metabolic phenotype comparable to young exercisers.
Asunto(s)
Ejercicio Físico/fisiología , Músculo Esquelético/enzimología , Consumo de Oxígeno , Aptitud Física/fisiología , Anciano , Composición Corporal , Femenino , Humanos , Masculino , Músculo Esquelético/irrigación sanguíneaRESUMEN
KEY POINTS: Synapses have high energy demands which increase during intense activity. We show that presynaptic terminals can utilise extracellular glucose or lactate to generate energy to maintain synaptic transmission. Reducing energy substrates induces a metabolic stress: presynaptic ATP depletion impaired synaptic transmission through a reduction in the number of functional synaptic vesicle release sites and a slowing of vesicle pool replenishment, without a consistent change in release probability. Metabolic function is compromised in many pathological conditions (e.g. stroke, traumatic brain injury and neurodegeneration). Knowledge of how synaptic transmission is constrained by metabolic stress, especially during intense brain activity, will provide insights to improve cognition following pathological insults. ABSTRACT: The synapse has high energy demands, which increase during intense activity. Presynaptic ATP production depends on substrate availability and usage will increase during activity, which in turn could influence transmitter release and information transmission. We investigated transmitter release at the mouse calyx of Held synapse using glucose or lactate (10, 1 or 0 mm) as the extracellular substrates while inducing metabolic stress. High-frequency stimulation (HFS) and recovery paradigms evoked trains of EPSCs monitored under voltage-clamp. Whilst postsynaptic intracellular ATP was stabilised by diffusion from the patch pipette, depletion of glucose increased EPSC depression during HFS and impaired subsequent recovery. Computational modelling of these data demonstrated a reduction in the number of functional release sites and slowed vesicle pool replenishment during metabolic stress, with little change in release probability. Directly depleting presynaptic terminal ATP impaired transmitter release in an analogous manner to glucose depletion. In the absence of glucose, presynaptic terminal metabolism could utilise lactate from the aCSF and this was blocked by inhibition of monocarboxylate transporters (MCTs). MCT inhibitors significantly suppressed transmission in low glucose, implying that lactate is a presynaptic substrate. Additionally, block of glycogenolysis accelerated synaptic transmission failure in the absence of extracellular glucose, consistent with supplemental supply of lactate by local astrocytes. We conclude that both glucose and lactate support presynaptic metabolism and that limited availability, exacerbated by high-intensity firing, constrains presynaptic ATP, impeding transmission through a reduction in functional presynaptic release sites as vesicle recycling slows when ATP levels are low.
Asunto(s)
Potenciales de Acción , Tronco Encefálico/fisiología , Glucosa/metabolismo , Ácido Láctico/metabolismo , Terminales Presinápticos/fisiología , Sinapsis/fisiología , Transmisión Sináptica , Animales , Tronco Encefálico/citología , Femenino , Masculino , Ratones , Ratones Endogámicos CBARESUMEN
In the brain, the postsynaptic response of a neuron to time-varying inputs is determined by the interaction of presynaptic spike times with the short-term dynamics of each synapse. For a neuron driven by stochastic synapses, synaptic depression results in a quite different postsynaptic response to a large population input depending on how correlated in time the spikes across individual synapses are. Here we show using both simulations and mathematical analysis that not only the rate but the phase of the postsynaptic response to a rhythmic population input varies as a function of synaptic dynamics and synaptic configuration. Resultant phase leads may compensate for transmission delays and be predictive of rhythmic changes. This could be particularly important for sensory processing and motor rhythm generation in the nervous system.
Asunto(s)
Potenciales de Acción/fisiología , Modelos Neurológicos , Plasticidad Neuronal/fisiología , Animales , Biología ComputacionalRESUMEN
Allelopathy among aquatic organisms, especially microorganisms, has received growing attention in recent years for its role in shaping interactions with bloom-forming algae. Many studies have shown that allelopathy occurs and increases under nutrient limiting conditions. However, to date there is no reported direct evidence to indicate that allelopathy occurs under the condition of constant high nutrient supply. Here we report the allelopathic action of periphytic biofilm on bloom-forming cyanobacteria (Microcystis aeruginosa), which was triggered by the stress of high nutrient conditions, and continues while nutrients are maintained at high levels (trophic state index at 159 and 171). The experimental evidence indicates that the electron transport from photosystem II (PS II) to photosystem I (PS I) in M. aeruginosa is interrupted by the identified allelochemicals, (9Z)-Octadec-9-enoic acid and (9Z)-Hexadec-9-enoic acid, leading to the failure of photosynthesis and the subsequent death of M. aeruginosa. Our findings indicate that the nutrient stress of constant high nutrient supply may be a newly recognized trigger causing allelopathy between microbial competitors, and therefore opening a new direction for the better management of ecological processes in cyanobacteria-dominated and hyper-eutrophic waters.
Asunto(s)
Alelopatía , Biopelículas , Microcystis , CianobacteriasRESUMEN
Cheating incidents in 2006-07 led U.S. dental schools to heighten their efforts to enhance the environment of academic integrity in their institutions. The aims of this study were to document the measures being used by U.S. dental schools to discourage student cheating, determine the current incidence of reported cheating, and make recommendations for enhancing a culture of integrity in dental education. In late 2014-early 2015, an online survey was distributed to academic deans of all 61 accredited U.S. dental schools that had four classes of dental students enrolled; 50 (82%) responded. Among measures used, 98% of respondents reported having policy statements regarding student academic integrity, 92% had an Honor Code, 96% provided student orientation to integrity policies, and most used proctoring of final exams (91%) and tests (93%). Regarding disciplinary processes, 27% reported their faculty members only rarely reported suspected cheating (though required in 76% of the schools), and 40% disseminated anonymous results of disciplinary hearings. A smaller number of schools (n=36) responded to the question about student cheating than to other questions; those results suggested that reported cheating had increased almost threefold since 1998. The authors recommend that schools add cheating case scenarios to professional ethics curricula; disseminate outcomes of cheating enforcement actions; have students sign a statement attesting to compliance with academic integrity policies at every testing activity; add curricular content on correct writing techniques to avoid plagiarism; require faculty to distribute retired test items; acquire examination-authoring software programs to enable faculty to generate new multiple-choice items and different versions of the same multiple-choice tests; avoid take-home exams when assessing independent student knowledge; and utilize student assessment methods directly relevant to clinical practice.
Asunto(s)
Decepción , Educación en Odontología , Ética Odontológica , Facultades de Odontología , Estudiantes de Odontología , Actitud del Personal de Salud , Educación en Odontología/ética , Evaluación Educacional , Humanos , Principios Morales , Política Organizacional , Facultades de Odontología/ética , Facultades de Odontología/organización & administración , Estudiantes de Odontología/psicología , Estados UnidosRESUMEN
Previous experimental data indicates the hyperpolarization-activated cation (Ih) current, in the inner ear, consists of two components [different hyperpolarization-activated cyclic nucleotide-gated (HCN) subunits] which are impossible to pharmacologically isolate. To confirm the presence of these two components in vestibular ganglion neurons we have applied a parameter identification algorithm which is able to discriminate the parameters of the two components from experimental data. Using simulated data we have shown that this algorithm is able to identify the parameters of two populations of non-inactivated ionic channels more accurately than a classical method. Moreover, the algorithm was demonstrated to be insensitive to the key parameter variations. We then applied this algorithm to Ih current recordings from mouse vestibular ganglion neurons. The algorithm revealed the presence of a high-voltage-activated slow component and a low-voltage-activated fast component. Finally, the electrophysiological significance of these two Ih components was tested individually in computational vestibular ganglion neuron models (sustained and transient), in the control case and in the presence of cAMP, an intracellular cyclic nucleotide that modulates HCN channel activity. The results suggest that, first, the fast and slow components modulate differently the action potential excitability and the excitatory postsynaptic potentials in both sustained and transient vestibular neurons and, second, the fast and slow components, in the control case, provide different information about characteristics of the stimulation and this information is significantly modified after modulation by cAMP.
Asunto(s)
Ganglios Sensoriales/fisiología , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/fisiología , Modelos Neurológicos , Neuronas/fisiología , Nervio Vestibular/fisiología , Potenciales de Acción , Algoritmos , Animales , Simulación por Computador , Femenino , Masculino , RatonesRESUMEN
A computational model of a biochemical network underlying synaptic plasticity is combined with simulated on-going electrical activity in a model of a hippocampal pyramidal neuron to study the impact of synapse location and inhibition on synaptic plasticity. The simulated pyramidal neuron is activated by the realistic stimulation protocol of causal and anticausal spike pairings of presynaptic and postsynaptic action potentials in the presence and absence of spatially targeted inhibition provided by basket, bistratified and oriens-lacunosum moleculare (OLM) interneurons. The resulting Spike-timing-dependent plasticity (STDP) curves depend strongly on the number of pairing repetitions, the synapse location and the timing and strength of inhibition.
Asunto(s)
Región CA1 Hipocampal/fisiología , Inhibición Neural/fisiología , Plasticidad Neuronal/fisiología , Células Piramidales/fisiología , Región CA1 Hipocampal/citología , Potenciales de la Membrana/fisiologíaRESUMEN
Cellular activity in the CA1 area of the hippocampus waxes and wanes at theta frequency (4-8 Hz) during exploratory behavior of rats. Perisomatic inhibition onto pyramidal cells tends to be strongest out of phase with pyramidal cell activity, whereas dendritic inhibition is strongest in phase with pyramidal cell activity. Synaptic plasticity also varies across the theta cycle, from strong long-term potentiation (LTP) to long-term depression (LTD), putatively corresponding to encoding and retrieval phases for information patterns encoded by pyramidal cell activity (Hasselmo et al. (2002a) Neural Comput 14:793-817). The mechanisms underpinning the phasic changes in plasticity are not clear, but it is likely that inhibition plays a role by affecting levels of electrical activity and calcium concentration at synapses. We explore the properties of synaptic plasticity during theta at Schaffer collateral synapses on CA1 pyramidal neurons and the influence of spatially and temporally targeted inhibition using a detailed multicompartmental model of the CA1 pyramidal neuron microcircuit and a phenomenological model of synaptic plasticity. The results suggest CA3-CA1 synapses are potentiated on one phase of theta due to high calcium levels provided by paired weak CA3 and layer III entorhinal cortex (EC) inputs even when somatic spiking is inhibited by perisomatic interneuron activity. Weak CA3 inputs alone induce lower calcium transients and result in depression of the CA3-CA1 synapses. These synapses are depressed if activated in phase with dendritic inhibition as strong CA3 inputs alone are not able to cause high calcium in this theta phase even though the CA1 pyramidal neuron shows somatic spiking. Dendritic inhibition acts as a switch that prevents LTP and promotes LTD during the retrieval phases of the theta rhythm in CA1 pyramidal cell. This may be important for not overly reinforcing recalled memories and in forgetting no longer relevant memories.
Asunto(s)
Región CA1 Hipocampal/fisiología , Modelos Neurológicos , Plasticidad Neuronal/fisiología , Células Piramidales/fisiología , Sinapsis/fisiología , Ritmo Teta/fisiología , Potenciales de Acción/fisiología , Animales , Región CA3 Hipocampal/fisiología , Calcio/metabolismo , Simulación por Computador , Corteza Entorrinal/fisiología , Interneuronas/fisiología , Inhibición Neural/fisiología , Vías Nerviosas/fisiologíaRESUMEN
We use a computational model of a hippocampal CA1 pyramidal cell to demonstrate that spine head calcium provides an instantaneous readout at each synapse of the postsynaptic weighted sum of all presynaptic activity impinging on the cell. The form of the readout is equivalent to the functions of weighted, summed inputs used in neural network learning rules. Within a dendritic layer, peak spine head calcium levels are either a linear or sigmoidal function of the number of coactive synapses, with nonlinearity depending on the ability of voltage spread in the dendrites to reach calcium spike threshold. This is strongly controlled by the potassium A-type current, with calcium spikes and the consequent sigmoidal increase in peak spine head calcium present only when the A-channel density is low. Other membrane characteristics influence the gain of the relationship between peak calcium and the number of active synapses. In particular, increasing spine neck resistance increases the gain due to increased voltage responses to synaptic input in spine heads. Colocation of stimulated synapses on a single dendritic branch also increases the gain of the response. Input pathways cooperate: CA3 inputs to the proximal apical dendrites can strongly amplify peak calcium levels due to weak EC input to the distal dendrites, but not so strongly vice versa. CA3 inputs to the basal dendrites can boost calcium levels in the proximal apical dendrites, but the relative electrical compactness of the basal dendrites results in the reverse effect being less significant. These results give pointers as to how to better describe the contributions of pre- and postsynaptic activity in the learning "rules" that apply in these cells. The calcium signal is closer in form to the activity measures used in traditional neural network learning rules than to the spike times used in spike-timing-dependent plasticity.
Asunto(s)
Calcio/metabolismo , Espinas Dendríticas/metabolismo , Modelos Neurológicos , Plasticidad Neuronal/fisiología , Neuronas/citología , Animales , Biofisica , Región CA1 Hipocampal/citología , Vías Nerviosas/fisiologíaRESUMEN
BACKGROUND AND OBJECTIVE: Oxygen is used in many clinical scenarios, however the variable performance of nasal cannulae makes determining the precise fraction of inspired oxygen (FiO2 ) difficult. We developed a novel method for measurement of the tracheal FiO2 using a catheter placed via bronchoscopy. We investigate the effects of oxygen delivery, respiratory rate, mouth position and estimated minute ventilation (VE ) on the FiO2 delivered by nasal cannulae. METHODS: The catheter was placed in 20 subjects. Tracheal gas concentrations were analysed during six 5-min treatments controlling for oxygen delivery rate, respiratory rate and mouth position. Ventilation was monitored with respiratory inductive plethysmography (RIP). The FiO2 delivered by nasal cannulae was compared between treatments, and we investigated the relationships among the FiO2 , alveolar partial pressure of oxygen (PA O2 ) and VE . RESULTS: The FiO2 increased by 0.038/L/min of oxygen. Respiratory rate had a significant effect on the FiO2 . A normal respiratory rate of 15 breaths/min and oxygen supplementation via nasal cannula at 2 L/min resulted in an FiO2 of 0.296; however, FiO2 decreased by 0.012 at 20 breaths/min and 0.004 at 10 breaths/min. The mean FiO2 decreased by 0.024 with the mouth open. The FiO2 and PA O2 were observed to decrease with increasing VE . CONCLUSIONS: Continuous measurement of the FiO2 using a transtracheal catheter provides detailed insight into inspiratory changes of the FiO2 delivered by nasal cannulae. Our study confirms that respiratory rate, VE and mouth position significantly influence the inspired oxygen concentration. These parameters should be accounted for when prescribing oxygen.
Asunto(s)
Broncoscopía/métodos , Intubación Intratraqueal/métodos , Terapia por Inhalación de Oxígeno , Oxígeno , Catéteres , Protocolos Clínicos , Monitoreo de Drogas/métodos , Humanos , Inhalación/fisiología , Oxígeno/administración & dosificación , Oxígeno/análisis , Terapia por Inhalación de Oxígeno/instrumentación , Terapia por Inhalación de Oxígeno/métodos , Pletismografía/métodos , Pruebas de Función Respiratoria/métodos , Frecuencia Respiratoria/fisiologíaRESUMEN
Two computational models are used to explore the possible implications of recent experimental data (Royer et al. 2012) on phasic inhibition during theta frequency (4-10 Hz) oscillations in the hippocampi of actively behaving rodents. A working hypothesis from previous experimental and modelling studies is that a theta cycle is divided into encoding (when synaptic plasticity is enhanced) and recall (when plasticity is suppressed) half cycles. Using a compartmental model of a CA1 pyramidal cell, including dendritic spines, we demonstrate that out-of-phase perisomatic and dendritic inhibition, respectively, can promote the necessary conditions for these half cycles. Perisomatic inhibition allows dendritic calcium spikes that promote synaptic LTP, while minimising cell output. Dendritic inhibition, on the other hand, both controls cell output and suppresses dendritic calcium spikes, preventing LTP. The exact phase relationship between these sub-cycles may not be fixed. Using a simple sum-of-sinusoids activity model, we suggest an interpretation of the data of Royer et al. (2012) in which a fixed-phase encoding sub-cycle is surrounded by a flexible-phase recall cycle that follows the peak of excitatory drive and consequent phase precession of activity as an animal passes through a pyramidal cell's place field.