RESUMO
PURPOSE: To be able to walk safely up or down a staircase, we must be able to judge the configuration and slope of the staircase and our viewing position. Adding markings to the stairs might help form correct perceptions of the staircase geometry. In this study, we examined how visual judgements about staircase configuration are affected by different marking patterns. METHODS: Fifteen normally sighted young participants viewed computer-generated images of staircases as seen from the top landing of the stairs. Marking patterns included contrasting baseboard, transverse edge-stripes, longitudinal side-stripes, longitudinal stripes, diamond patterns, longitudinal stripes extended to landing and diamond patterns extended to landing. For comparison, we included the no-marking condition as a control. We tested several contrast levels of marking patterns (3.2%-50%), pitch lines of the staircases (shallow/medium/steep) and viewing positions (left/centre/right). The effect of the overall shape cue of the staircase on participants' performance was also evaluated. We measured participants' accuracies in judging whether the staircase was shallow, medium or steep, and whether the viewing position was located to the left, centre or right. RESULTS: Transverse edge-stripes markings yielded fewer underestimations of slope (9% [transverse] vs. 18% [others]) when compared with other markers. The presence of an overall shape cue helped both slope (67% [presence] vs. 51% [absence]) and viewing position judgements (79% [presence] vs. 62% [absence]). When the overall shape cue was present, only the transverse edge-stripes markings yielded a significant improvement in performance (compared with no-marking condition). When the cue was absent, performance was significantly better with markings with high and moderate contrasts. CONCLUSIONS: Adding marking patterns such as high-contrast transverse stripes to stairs may help enhance the visibility of the stairs and judgements of staircase geometry. This might be particularly useful for people with visual impairment or normally sighted individuals under compromised environmental conditions.
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Sensibilidades de Contraste , Acuidade Visual , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Sensibilidades de Contraste/fisiologia , Acuidade Visual/fisiologia , Sinais (Psicologia) , Estimulação Luminosa/métodos , Caminhada/fisiologiaRESUMO
Changes in biodiversity at all levels from molecules to ecosystems are often linked to climate change, which is widely represented univariately by temperature. A global environmental driving mechanism of biodiversity dynamics is thus implied by the strong correlation between temperature proxies and diversity patterns in a wide variety of fauna and flora. Yet climate consists of many interacting variables. Species probably respond to the entire climate system as opposed to its individual facets. Here, we examine ecological and morphological traits of 12 633 individuals of two species of planktonic foraminifera with similar ecologies but contrasting evolutionary outcomes. Our results show that morphological and ecological changes are correlated to the interactions between multiple environmental factors. Models including interactions between climate variables explain at least twice as much variation in size, shape and abundance changes as models assuming that climate parameters operate independently. No dominant climatic driver can be identified: temperature alone explains remarkably little variation through our highly resolved temporal sequences, implying that a multivariate approach is required to understand evolutionary response to abiotic forcing. Our results caution against the use of a 'silver bullet' environmental parameter to represent global climate while studying evolutionary responses to abiotic change, and show that more comprehensive reconstruction of palaeobiological dynamics requires multiple biotic and abiotic dimensions.
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Evolução Biológica , Mudança Climática , Foraminíferos/citologia , Foraminíferos/fisiologia , Características de História de Vida , Animais , Temperatura , Zooplâncton/citologia , Zooplâncton/fisiologiaRESUMO
Erosion, sediment production, and routing on a tectonically active continental margin reflect both tectonic and climatic processes; partitioning the relative importance of these processes remains controversial. Gulf of Alaska contains a preserved sedimentary record of the Yakutat Terrane collision with North America. Because tectonic convergence in the coastal St. Elias orogen has been roughly constant for 6 My, variations in its eroded sediments preserved in the offshore Surveyor Fan constrain a budget of tectonic material influx, erosion, and sediment output. Seismically imaged sediment volumes calibrated with chronologies derived from Integrated Ocean Drilling Program boreholes show that erosion accelerated in response to Northern Hemisphere glacial intensification (â¼ 2.7 Ma) and that the 900-km-long Surveyor Channel inception appears to correlate with this event. However, tectonic influx exceeded integrated sediment efflux over the interval 2.8-1.2 Ma. Volumetric erosion accelerated following the onset of quasi-periodic (â¼ 100-ky) glacial cycles in the mid-Pleistocene climate transition (1.2-0.7 Ma). Since then, erosion and transport of material out of the orogen has outpaced tectonic influx by 50-80%. Such a rapid net mass loss explains apparent increases in exhumation rates inferred onshore from exposure dates and mapped out-of-sequence fault patterns. The 1.2-My mass budget imbalance must relax back toward equilibrium in balance with tectonic influx over the timescale of orogenic wedge response (millions of years). The St. Elias Range provides a key example of how active orogenic systems respond to transient mass fluxes, and of the possible influence of climate-driven erosive processes that diverge from equilibrium on the million-year scale.
RESUMO
The influence of within-species variation and covariation on evolutionary patterns is well established for generational and macroevolutionary processes, most prominently through genetic lines of least resistance. However, it is not known whether intraspecific phenotypic variation also directs microevolutionary trajectories into the long term when a species is subject to varying environmental conditions. Here we present a continuous, high-resolution bivariate record of size and shape changes among 12,633 individual planktonic foraminifera of a surviving and an extinct-going species over 500,000 years. Our study interval spans the late Pliocene to earliest Pleistocene intensification of northern hemisphere glaciation, an interval of profound climate upheaval that can be divided into three phases of increasing glacial intensity. Within each of these three Plio-Pleistocene climate phases, the within-population allometries predict evolutionary change from one time step to the next and that the within-phase among-population (i.e., evolutionary) allometries match their corresponding static (within-population) allometries. However, the evolutionary allometry across the three climate phases deviates significantly from the static and phase-specific evolutionary allometries in the extinct-going species. Although intraspecific variation leaves a clear signature on mean evolutionary change from one time step to the next, our study suggests that the link between intraspecific variation and longer-term micro- and macroevolutionary phenomena is prone to environmental perturbation that can overcome constraints induced by within-species trait covariation.
Assuntos
Evolução Biológica , Meio Ambiente , Fenótipo , Animais , ClimaRESUMO
BACKGROUND: The United Kingdom population is ageing. Half of patients requiring an emergency laparotomy are aged over 70, 20 % die within 30 days, and less than half receive good care. Frailty and delay in management are associated with poor surgical outcomes. P-POSSUM risk scoring is widely accepted, but its validity in patients aged over 70 undergoing emergency laparotomy is unclear. AIMS: To assess if P-POSSUM risk stratification reliably predicts inpatient mortality in this group and establish whether those who died within 30 days received delayed care. METHODS: Observational study of consecutive patients aged 70 and over fulfilling the National Emergency Laparotomy Audit criteria from a tertiary hospital. The predictive value of pre-operative P-POSSUM, ASA, lactate and other routine variables was assessed. Surgical review, decision to operate, consultant surgical review, antibiotic prescription, laparotomy and discharge or death time points were assessed by 30-day survival. RESULTS: One hundred and ninety-three patients were included. This represented 46.28 % of those undergoing an emergency laparotomy in our centre. Pre-operative P-POSSUM scoring, ASA grade and lactate were moderate predictors of mortality (AUC 0.784 and 0.771, respectively, lactate AUC 0.705, all p ≤ 0.001). No correlation existed between pre-operative P-POSSUM and days to death (p = 0.209), nor were there delays in key management timings in those who died in 30 days. CONCLUSIONS: P-POSSUM scoring may predict inpatient mortality with moderate discrimination. Addition of frailty scoring in this high-risk group might better identify those with a high risk of mortality after emergency laparotomy and would be a fertile area for further research.
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Abdome/cirurgia , Emergências , Mortalidade Hospitalar , Laparotomia/mortalidade , Medição de Risco , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Ácido Láctico/sangue , Masculino , Reino Unido/epidemiologiaRESUMO
PURPOSE: Hydrogen sulfide (H2S) is a highly toxic gas with well-established, acute irritation effects on the eye. The population of Rotorua, New Zealand, sited on an active geothermal field, has some of the highest ambient H2S exposures in the world. Evidence from ecological studies in Rotorua has suggested that H2S is associated with cataract. The purpose of the present study was, using more detailed exposure characterization, clinical examinations, and anterior eye photography, to more directly investigate this previously reported association. METHODS: Enrolled were 1637 adults, ages 18 to 65, from a comprehensive Rotorua primary care medical register. Patients underwent a comprehensive ophthalmic examination, including pupillary dilation and lens photography to capture evidence of any nuclear opacity, nuclear color, and cortical and posterior subcapsular opacity. Photographs were scored for all four outcomes on the LOCS III scale with decimalized interpolation between the exemplars. H2S exposure for up to the last 30 years was estimated based on networks of passive samplers set out across Rotorua and knowledge of residential, workplace, and school locations over the 30 years. Data analysis using linear and logistic regression examined associations between the degree of opacification and nuclear color or cataract (defined as a LOCS III score ≥2.0) in relation to H2S exposure. RESULTS: No associations were found between estimated H2S exposures and any of the four ophthalmic outcome measures. CONCLUSIONS: Overall, results were generally reassuring. They provided no evidence that H2S exposure at the levels found in Rotorua is associated with cataract. The previously found association between cataract and H2S exposure in the Rotorua population seems likely to be attributable to the limitations of the ecological study design. These results cannot rule out the possibility of an association with cataract at higher levels of H2S exposure.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Catarata/induzido quimicamente , Exposição Ambiental/efeitos adversos , Fontes Termais , Sulfeto de Hidrogênio/efeitos adversos , Cristalino/efeitos dos fármacos , Adolescente , Adulto , Idoso , Catarata/epidemiologia , Feminino , Fontes Termais/química , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Nível de Efeito Adverso não Observado , Fotografação , Fatores de Risco , Adulto JovemRESUMO
PURPOSE: To assess whether the slopes of psychometric functions for measuring low contrast letter acuity were different from those for measuring high contrast letter acuity. METHODS: Ten participants, wearing their best spectacle correction, were assessed monocularly. Stimuli were logarithmic progression charts, generated on a computer monitor, with nine rows of five randomised Sloan letters generated in either high contrast format (Weber contrast 99.2%) or low contrast format (Weber contrast 18.7%). For each participant, psychometric functions were generated by probit analysis of the data on each of 16 attempts at a low contrast chart and 16 attempts at a high contrast chart. Each of these probit fits yielded an estimate of Probit Size which provided information about how steep or flat the psychometric function was, along with an estimate of Probit Acuity Threshold. RESULTS: Probit Size was significantly larger (p < 0.001) for low contrast charts than for high contrast charts, indicating that psychometric functions were flatter for low contrast charts. Mean Probit Sizes in logMAR were 0.099 (SEM 0.022) for low contrast charts and 0.071 (SEM 0.009) for high contrast charts if a guess rate of 1/26 was assumed, or were 0.086 (SEM 0.019) for low contrast charts and 0.064 for high contrast charts if a guess rate of 1/10 was assumed. Monte Carlo analysis showed that these means were likely to be biased estimates, with true Probit Size probably being larger (i.e. slightly flatter fits) by 0.016-0.019 logMAR. As expected, Probit Acuity Thresholds were poorer for low contrast charts than for high contrast charts (p < 0.001). CONCLUSION: Our Monte Carlo modelling showed that such differences in acuity psychometric functions would be expected to give greater intra-subject variability in low contrast letter-by-letter acuity thresholds than for high contrast letter-by-letter acuity thresholds, and that this difference would depend on the termination rule used when measuring acuity. Likewise the variation in letter-by- letter acuity thresholds with termination rule will be different for high and low contrast charts. For low contrast and high contrast Sloan letter charts in a standard logarithmic format, a termination rule of four mistakes on a row, will give close to optimum sensitivity-to-change.
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Sensibilidades de Contraste/fisiologia , Psicometria/métodos , Testes Visuais/instrumentação , Acuidade Visual/fisiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método de Monte Carlo , Adulto JovemRESUMO
BACKGROUND: Oesophageal adenocarcinoma (OAC) is increasingly common in the west, and survival remains poor at 10-15 % at 5 years. Immune responses are increasingly implicated as a determining factor of tumour progression. The ability of lymphocytes to recognise tumour antigens provides a mechanism for a host immune attack against cancer providing a potential treatment strategy. MATERIALS AND METHODS: Tumour infiltrating lymphocytes (TILs: CD3+, CD4+, CD8+ and FOXp3+) were assessed by immunohistochemistry using tissue microarrays in a contemporary and homogeneous cohort of OAC patients (n = 128) undergoing curative treatment. RESULTS: Multivariate analysis identified three independent prognostic factors for improved cancer-specific survival (CSS): increased CD8+ TILs (p = 0.003), completeness of resection (p < 0.0001) and lower pathological N stage (p < 0.0001). Independent prognostic factors for favourable disease-free survival included surgery-only treatment (p = 0.015), completeness of resection (p = 0.001), increased CD8+ TILs (p < 0.0001) and reduced pathological N stage (p < 0.0001). Higher levels of TILs in the pathological specimen were associated with significant pathological response to neoadjuvant chemotherapy (NAC). On multivariate analysis increased levels of CD4+ (p = 0.017) and CD8+ TILs (p = 0.005) were associated with significant local tumour regression and lymph node downstaging, respectively. DISCUSSION: Our results establish an association of TILs and survival in OAC, as seen in other solid tumours, and identify particular TIL subsets that are present at higher levels in patients who responded to NAC compared to non-responders. These findings highlight potential therapeutic strategies in EAC based on utilising the host immunological response and highlight the immune responses biomarker potential.
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Adenocarcinoma/imunologia , Adenocarcinoma/mortalidade , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/mortalidade , Linfócitos do Interstício Tumoral/imunologia , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Terapia Combinada , Progressão da Doença , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Estimativa de Kaplan-Meier , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Subpopulações de Linfócitos/patologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Carga TumoralRESUMO
The endoplasmic reticulum aminopeptidase associated with Ag processing, ERAAP, plays an important role in the trimming of antigenic peptides for presentation at the cell surface complexed with MHC class I molecules. Tumors express varying levels of ERAAP, highlighting a possible mechanism of immune-evasion through alteration of the peptide repertoire. Using the CT26 tumor model, we investigated the effects of ERAAP modulation on peptide presentation and the use of ERAAP inhibition as an antitumor therapy. We show that generation of the cross-protective tumor Ag GSW11 in the colorectal carcinoma CT26 is increased when ERAAP expression is reduced. BALB/c mice with reduced ERAAP expression challenged with CT26 induced protective immunity that was mediated by CD8(+) T cells. This antitumor immunity also protected mice when rechallenged with wild-type CT26 tumor; strong CD8(+) T cell responses to GSW11 were observed, despite its presentation being considerably lower. Furthermore, boosting the tumor immunogenicity through inhibition of ERAAP function with the small molecule inhibitor leucinethiol in vitro, or in established tumors in vivo, abrogated tumor growth and prolonged survival. Thus, our results highlight the promising possibility of using modulation of ERAAP to generate protective antitumor responses as a strategy for cancer immunotherapy.
Assuntos
Leucil Aminopeptidase/metabolismo , Neoplasias/imunologia , Neoplasias/metabolismo , Animais , Apresentação de Antígeno , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Inibidores Enzimáticos/farmacologia , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Inativação Gênica , Humanos , Leucil Aminopeptidase/antagonistas & inibidores , Leucil Aminopeptidase/genética , Camundongos , Neoplasias/genética , Neoplasias/mortalidadeRESUMO
INTRODUCTION: The Siewert classification has been used to plan treatment for tumours of the gastro-oesophageal junction since its proposal in the 1980s. The purpose of this study was to assess its continued relevance by evaluating whether there were differences in the biology and clinical characteristics of adenocarcinomas by Siewert type, in a contemporary cohort of patients, in whom the majority had received neoadjuvant chemotherapy. METHODS: A prospective database was reviewed for all patients who underwent resection from 2005 to 2011 and analysed with regard to Siewert classification determined from the pathological specimen, treatment and clinicopathological outcomes. RESULTS: Two hundred and sixteen patients underwent oesophagogastric resection: 133 for type I, 51 for type II and 33 for type III tumours. 135 Patients (62.5%) received neoadjuvant chemotherapy with no difference between groups. There were no significant differences in age, sex, pT stage, pN stage, pM stage, ASA, or inpatient complications between patients with adenocarcinoma based on their Siewert classification. There was a significant increase in maximum tumour diameter (P = 0.023), perineural invasion (P = 0.021) and vascular invasion (P = 0.020), associated with more distal tumours (Type III > Type II > Type I). Median overall survival was significantly shorter for more distal tumours (Type I: 4.96 years vs. Type II: 3.3 years vs. Type III: 2.64 years; P = 0.04). The surgical approach did not influence survival. CONCLUSION: In the era of multi-modal treatment pathological Siewert tumour type is of prognostic value, as patients with Type III disease are likely to have larger and more aggressive tumours that lead to worse outcomes.
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Adenocarcinoma/classificação , Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/classificação , Neoplasias Esofágicas/terapia , Junção Esofagogástrica/cirurgia , Neoplasias Gástricas/classificação , Neoplasias Gástricas/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fístula Anastomótica/etiologia , Capecitabina , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Bases de Dados Factuais , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Epirubicina/administração & dosagem , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Junção Esofagogástrica/patologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Hospitais Universitários , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Reino Unido/epidemiologiaRESUMO
PURPOSE: At a fixed viewing distance (VD), reading speed increases with print size. It is not known if this holds for computer tasks when postures are not constrained. Reflective glare on a monitor may reduce productivity. The effects of both may be modified by age. We evaluated effects of age, font size, and glare on performance for visually demanding text-based tasks on a computer. METHODS: Nineteen young (18 to 35 years old) and eight older (55 to 65 years old wearing progressive lenses that correct for presbyopia) subjects participated in a study with two trial factors: font size (1.78, 2.23, and 3.56 mm) and glare (produced by bright light-emitting diode task light reflective off a matte liquid crystal display monitor). The monitor location was fixed but subjects were allowed to change their posture and move the chair. Subjects performed visual tasks that required similar visual skills to common tasks such as Internet use, data entry, or word processing. RESULTS: Productivity, accuracy, and VD increased as font size increased. For each 1-mm increase in font size, there was a mean productivity gain of 3 correct clicks/min and an improvement in accuracy of 2%. Font size increase also led to lowered perceived task difficulty. Adding reflective glare on the monitor surface led to a reduced VD but had no effect on productivity or accuracy. With visual corrections for presbyopia, age had no effect on these relationships. CONCLUSIONS: Productivity is improved when the font is increased from 1.78 or 2.23 to 3.56 mm for text-based computer tasks. The largest font size corresponds to a visual angle of font of 23.4 arcmin. This visual angle of font is above the high end of ISO recommendations (International Organization for Standardization, 1992, 2011). The findings may be useful for setting the font sizes for computers and for training office workers.
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Envelhecimento/fisiologia , Terminais de Computador , Ofuscação , Impressão/instrumentação , Leitura , Análise e Desempenho de Tarefas , Adolescente , Adulto , Idoso , Ergonomia , Óculos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Presbiopia/terapia , Acuidade Visual/fisiologia , Adulto JovemRESUMO
PURPOSE: Cataract is the most prevalent cause of blindness in Nepal. Several epidemiologic studies have associated cataracts with use of biomass cookstoves. These studies, however, have had limitations, including potential control selection bias and limited adjustment for possible confounding. This study, in Pokhara City, in an area of Nepal where biomass cookstoves are widely used without direct venting of the smoke to the outdoors, focuses on preclinical measures of opacity while avoiding selection bias and taking into account comprehensive data on potential confounding factors. METHODS: Using a cross-sectional study design, severity of lenticular damage, judged on the LOCS (Lens Opacities Classification System) III scales, was investigated in women (n = 143), aged 20 to 65 years, without previously diagnosed cataract. Linear and logistic regression analyses were used to examine the relationships with stove type and length of use. Clinically significant cataract, used in the logistic regression models, was defined as a LOCS III score ≥2. RESULTS: Using gas cookstoves as the reference group, logistic regression analysis for nuclear cataract showed evidence of relationships with stove type: for biomass stoves, the odds ratio was 2.58 (95% confidence interval, 1.22 to 5.46); and for kerosene stoves, the odds ratio was 5.18 (95% confidence interval, 0.88 to 30.38). Similar results were found for nuclear color (LOCS III score ≥2), but no association was found with cortical cataracts. Supporting a relationship between biomass stoves and nuclear cataract was a trend with years of exposure to biomass cookstoves (p = 0.01). Linear regression analyses did not show clear evidence of an association between lenticular damage and stove types. Biomass fuel used for heating was not associated with any form of opacity. CONCLUSIONS: This study provides support for associations of biomass and kerosene cookstoves with nuclear opacity and change in nuclear color. The novel associations with kerosene cookstove use deserve further investigation.
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Biomassa , Catarata/epidemiologia , Exposição Ambiental/efeitos adversos , Utensílios Domésticos , Cristalino/patologia , Adulto , Idoso , Catarata/etiologia , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Nepal/epidemiologia , Prevalência , Fatores de Risco , Adulto JovemRESUMO
In fishes, the C-start behavior, initiated with a C-shaped body bend, is a taxonomically common and widely studied escape response. Its simple neural circuit has made this behavior a model for examining neural control of movement. The S-start, initiated with an S-shaped body bend, is a physiologically distinct escape that occurs in esocid fishes. Here we examine whether zebrafish larvae perform S-starts in order to better understand startle diversity and to attempt to identify the S-start in a system that is tractable for neurobiological studies. We found that larval zebrafish startles varied in the extent of their caudal bending, resulting in C, S and intermediate-shaped responses. We recorded two distinct motor patterns: nearly simultaneous initial activity along one side of the body, characteristic of C-starts, and nearly simultaneous activity rostrally on one side and caudally on the other, characteristic of S-starts. Head stimulation generally elicited C-starts while tail stimulation elicited C- and S-starts. These results demonstrate that the S-start is more common than previously documented and occurs in early developmental stages. We suggest that the S-start may be a fundamental escape behavior in fishes and may provide a comparative model to the C-start for understanding simple neural circuits.
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Atividade Motora/fisiologia , Reflexo de Sobressalto/fisiologia , Natação/fisiologia , Peixe-Zebra/fisiologia , Animais , Estimulação Elétrica/métodos , Larva , Rede Nervosa/fisiologia , Estimulação Física/métodosRESUMO
In the CT26 BALB/c murine model of colorectal carcinoma, depletion of regulatory T cells (Tregs) prior to tumor inoculation results in protective immunity to both CT26 and other BALB/c-derived tumors of diverse histological origin. In this paper, we show that cross-protection can be conferred by adoptively transferred CD8(+) CTLs. Other schedules for inducing immunity to CT26 have been described, but they do not lead to cross-protection. We show that Treg ablation facilitates the development of new CTL specificities that are normally cryptic, and have mapped the root epitope of one of these responses. This work has allowed us to demonstrate how the specificity of CTL responses to tumor Ags can be controlled via differential suppression of CTL specificities by Tregs, and how this can result in very different physiological outcomes.
Assuntos
Antígenos de Neoplasias/imunologia , Linfócitos T CD8-Positivos/imunologia , Neoplasias Experimentais/imunologia , Linfócitos T Reguladores/imunologia , Transferência Adotiva , Animais , Linhagem Celular Tumoral , Reações Cruzadas , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Research and clinical papers in the ophthalmic literature commonly report visual acuity data. There is considerable variation in the way visual acuity measurements are expressed, and frequently, the charts and the procedures used for the visual acuity testing are inadequately described. Materials and methods can significantly affect visual acuity scores. Contributions to the scientific and professional literature should provide enough detail about their methodologies to allow others to replicate their studies. Here we call for authors and clinicians to be more careful about defining their term, to specifically identify their testing materials, and to give detailed descriptions of their methods of testing.
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Optometria , Testes Visuais/métodos , Acuidade Visual , HumanosRESUMO
PURPOSE: Very poor visual acuity often cannot be measured with letter charts even at close viewing distances. The Berkeley Rudimentary Vision Test (BRVT) was developed as a simple test to extend the range of visual acuity measurement beyond the limits of letter charts by systematically simplifying the visual task and using close viewing distances to achieve large angular sizes. The test has three pairs of hinged cards, 25 cm square. One card-pair has four single tumbling E (STE) optotypes at sizes 100 M, 63 M, 40 M, and 25 M. Another card-pair has four grating acuity (GA) targets at sizes 200 M, 125 M, 80 M, and 50 M. The third card-pair has a test of white field projection (WFP) and a test of black white discrimination (BWD). As a demonstration of feasibility, a population of subjects with severe visual impairment was tested with the BRVT. METHODS: Adults with severe visual impairments from a wide variety of causes were recruited from three different rehabilitation programs. Vision measurements were made on 54 eyes from 37 subjects; test administration times were measured. RESULTS: For this population, letter chart visual acuity could be measured on 24 eyes. Measurements of visual acuity for STE targets were made for 18 eyes and with GA targets, for two eyes. Five eyes had WFP, and one had BWD. Four had light perception only. The median testing time with the BRVT was 2.5 min. DISCUSSION: The BRVT extends the range of visual acuity up to logMAR = 2.60 (20/8000) for STEs, to logMAR = 2.90 (20/16,000) for gratings and includes the WFP and BWD tests. CONCLUSIONS: The BRVT is a simple and efficient test of spatial vision that, with 13 increments, extends the range of measurement from the limits of the letter chart up to light perception.
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Ambliopia/diagnóstico , Testes Visuais/métodos , Acuidade Visual , Adulto , Ambliopia/fisiopatologia , California , Humanos , MasculinoRESUMO
Antarctica is one of the most vulnerable regions to climate change on Earth and studying the past and present responses of this polar marine ecosystem to environmental change is a matter of urgency. Sedimentary ancient DNA (sedaDNA) analysis can provide such insights into past ecosystem-wide changes. Here we present authenticated (through extensive contamination control and sedaDNA damage analysis) metagenomic marine eukaryote sedaDNA from the Scotia Sea region acquired during IODP Expedition 382. We also provide a marine eukaryote sedaDNA record of ~1 Mio. years and diatom and chlorophyte sedaDNA dating back to ~540 ka (using taxonomic marker genes SSU, LSU, psbO). We find evidence of warm phases being associated with high relative diatom abundance, and a marked transition from diatoms comprising <10% of all eukaryotes prior to ~14.5 ka, to ~50% after this time, i.e., following Meltwater Pulse 1A, alongside a composition change from sea-ice to open-ocean species. Our study demonstrates that sedaDNA tools can be expanded to hundreds of thousands of years, opening the pathway to the study of ecosystem-wide marine shifts and paleo-productivity phases throughout multiple glacial-interglacial cycles.
Assuntos
Diatomáceas , Regiões Antárticas , DNA Antigo , Diatomáceas/genética , Ecossistema , Eucariotos , Sedimentos GeológicosRESUMO
Ice loss in the Southern Hemisphere has been greatest over the past 30 years in West Antarctica. The high sensitivity of this region to climate change has motivated geologists to examine marine sedimentary records for evidence of past episodes of West Antarctic Ice Sheet (WAIS) instability. Sediments accumulating in the Scotia Sea are useful to examine for this purpose because they receive iceberg-rafted debris (IBRD) sourced from the Pacific- and Atlantic-facing sectors of West Antarctica. Here we report on the sedimentology and provenance of the oldest of three cm-scale coarse-grained layers recovered from this sea at International Ocean Discovery Program Site U1538. These layers are preserved in opal-rich sediments deposited â¼1.2 Ma during a relatively warm regional climate. Our microCT-based analysis of the layer's in-situ fabric confirms its ice-rafted origin. We further infer that it is the product of an intense but short-lived episode of IBRD deposition. Based on the petrography of its sand fraction and the Phanerozoic 40Ar/39Ar ages of hornblende and mica it contains, we conclude that the IBRD it contains was likely sourced from the Weddell Sea and/or Amundsen Sea embayment(s) of West Antarctica. We attribute the high concentrations of IBRD in these layers to "dirty" icebergs calved from the WAIS following its retreat inland from its modern grounding line. These layers also sit at the top of a â¼366-m thick Pliocene and early Pleistocene sequence that is much more dropstone-rich than its overlying sediments. We speculate this fact may reflect that WAIS mass-balance was highly dynamic during the â¼41-kyr (inter)glacial world.
RESUMO
The Southern Ocean paleoceanography provides key insights into how iron fertilization and oceanic productivity developed through Pleistocene ice-ages and their role in influencing the carbon cycle. We report a high-resolution record of dust deposition and ocean productivity for the Antarctic Zone, close to the main dust source, Patagonia. Our deep-ocean records cover the last 1.5 Ma, thus doubling that from Antarctic ice-cores. We find a 5 to 15-fold increase in dust deposition during glacials and a 2 to 5-fold increase in biogenic silica deposition, reflecting higher ocean productivity during interglacials. This antiphasing persisted throughout the last 25 glacial cycles. Dust deposition became more pronounced across the Mid-Pleistocene Transition (MPT) in the Southern Hemisphere, with an abrupt shift suggesting more severe glaciations since ~0.9 Ma. Productivity was intermediate pre-MPT, lowest during the MPT and highest since 0.4 Ma. Generally, glacials experienced extended sea-ice cover, reduced bottom-water export and Weddell Gyre dynamics, which helped lower atmospheric CO2 levels.