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The evolution of lunge feeding in rorqual whales was associated with the evolution of several unique morphological features that include non-synovial ligamentous temporomandibular joints, a tongue that can invert and extend backward to the umbilicus, walls of the oral cavity that can dramatically expand, and muscles and nerves that are stretchy. Also, among the acquired features was an enlargement of the rostral end of the soft palate into an oral plug that occludes the opening between the oral cavity and pharynx and prevents water incursion into the pharynx during the engulfment phase of a feeding lunge. During this engulfment phase of a lunge, the volume of water entering the oral cavity can exceed the volume of the whale itself. Here, using dissection of fetuses and adults and a magnetic resonance imaging dataset of a fetus, we examine the detailed anatomy of the soft palate in fin whales. We describe several innovative features relative to other mammals, including changes in the attachment and positions of the major extrinsic muscles of the palate, alterations in the morphology of the pterygoid processes related to the palate and pharynx, and the presence of distinct muscle layers in the part of the palate caudal to the oral plug. Based on the anatomy, we present a model for how the soft palate is positioned at rest, and how it functions during feeding, breathing, and swallowing.
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Objective.To decipher brain network dynamic remodeling from electroencephalography (EEG) during a complex postural control (PC) task combining virtual reality and a moving platform.Approach.EEG (64 electrodes) data from 158 healthy subjects were acquired. The experiment is divided into several phases, and visual and motor stimulation is applied progressively. We combined advanced source-space EEG networks with clustering algorithms to decipher the brain networks states (BNSs) that occurred during the task.Main results.The results show that BNS distribution describes the different phases of the experiment with specific transitions between visual, motor, salience, and default mode networks coherently. We also showed that age is a key factor that affects the dynamic transition of BNSs in a healthy cohort.Significance.This study validates an innovative approach, based on a robust methodology and a consequent cohort, to quantify the brain networks dynamics in the BioVRSea paradigm. This work is an important step toward a quantitative evaluation of brain activities during PC and could lay the foundation for developing brain-based biomarkers of PC-related disorders.
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Encéfalo , Fenómenos Fisiológicos del Sistema Nervioso , Humanos , Encéfalo/fisiología , Electroencefalografía/métodos , Mapeo Encefálico , Equilibrio Postural , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: Species- and genetic diversity can change in parallel, resulting in a species-genetic diversity correlation (SGDC) and raising the question if the same drivers influence both biological levels of diversity. The SGDC can be either positive or negative, depending on whether the species diversity and the genetic diversity of the measured species respond in the same or opposite way to drivers. Using a traditional species diversity approach together with ultra-conserved elements and high throughput sequencing, we evaluated the SGDCs in benthic macrofauna communities in the Baltic Sea, a geologically young brackish water sea characterised by its steep salinity gradient and low species richness. Assessing SGDCs from six focal marine invertebrate species from different taxonomic groups and with differing life histories and ecological functions on both a spatial and temporal scale gives a more comprehensive insight into the community dynamics of this young ecosystem and the extrinsic factors that might drive the SGDCs. RESULTS: No significant correlations between species diversity and genetic diversity were found for any of the focal species. However, both negative and positive trends of SGDCs for the individual focal species were observed. When examining the environmental drivers, no common trends between the species were found, even when restricting the analysis to specific taxonomic classes. Additionally, there were no common environmental factors driving the diversity relationships for species sharing the same SGDC trend (positive or negative). Local population dynamics, together with the invasion history of the individual species and their unique adaptation to the distinctive environment of the Baltic Sea, are expected to be of major influence on the outcome of the SGDCs. CONCLUSIONS: The present results highlight the importance of assessing SGDCs using multiple species, not just a single indicator species. This emphasises a need to pay attention to the ecology and life history of the focal species. This study also provides insight into the large differences in both patterns and drivers of genetic diversity, which is important when including genetic biodiversity in conservation plans. We conclude that the effects of environmental and biological factors and processes that affects diversity patterns at both the community and genetic levels are likely species dependent, even in an environment such as the Baltic Sea with strong environmental gradients.
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Ecosistema , Salinidad , Animales , Biodiversidad , Invertebrados/genética , Variación Genética/genéticaRESUMEN
Objective.To define a new neurophysiological signature from electroencephalography (EEG) during a complex postural control task using the BioVRSea paradigm, consisting of virtual reality (VR) and a moving platform, mimicking the behavior of a boat on the sea.Approach.EEG (64 electrodes) data from 190 healthy subjects were acquired. The experiment is composed of 6 segments (Baseline, PRE, 25%, 50%, 75%, POST). The baseline lasts 60 s while standing on the motionless platform with a mountain view in the VR goggles. PRE and POST last 40 s while standing on the motionless platform with a sea simulation. The 3 other tasks last 40 s each, with the platform moving to adapt to the waves, and the subject holding a bar to maintain its balance. The power spectral density (PSD) difference for each task minus baseline has been computed for every electrode, for five frequency bands (delta, theta, alpha, beta, and low-gamma). Statistical significance has been computed.Main results.All the bands were significant for the whole cohort, for each task regarding baseline. Delta band shows a prefrontal PSD increase, theta a fronto-parietal decrease, alpha a global scalp power decrease, beta an increase in the occipital and temporal scalps and a decrease in other areas, and low-gamma a significant but slight increase in the parietal, occipital and temporal scalp areas.Significance.This study develops a neurophysiological reference during a complex postural control task. In particular, we found a strong localized activity associated with certain frequency bands during certain phases of the experiment. This is the first step towards a neurophysiological signature that can be used to identify pathological conditions lacking quantitative diagnostics assessment.
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Electroencefalografía , Equilibrio Postural , Humanos , Electroencefalografía/métodos , Equilibrio Postural/fisiologíaRESUMEN
Toxoplasma gondii is a zoonotic protozoan parasite capable of infecting possibly all warm-blooded animals including humans, and is one of the most widespread zoonotic pathogens known. Free-ranging wildlife can be valuable sentinels for oocyst contaminated environments, as well as a potential source for human foodborne infection with T. gondii. Here we aimed to determine the sero-prevalence of T. gondii in Danish wild deer populations and examine risk factors associated with increased exposure to the parasite. Blood samples were collected from 428 cervids (87 fallow deer (Dama dama), 272 red deer (Cervus elaphus), 55 roe deer (Capreolus capreolus) and 14 sika deer (Cervus Nippon) from 23 hunting sites in Denmark. The animals were shot during the hunting season 2017/2018, and screened for antibodies against T. gondii using a commercial ELISA kit. One hundred and five (24.5%) cervids were sero-positive. Sero-prevalence was significantly different between species (p < 0.05), with odds of sero-positivity being 4.5 times higher in roe deer than fallow deer, and 3.0 times higher in red deer than in fallow deer. A significant increase in sero-prevalence with age was observed, driven by a significant increase in risk in adult red deer compared to calves (OR: 13.22; 95% CI: 5.96-33.7). The only other significant risk factor associated with wild cervid T. gondii sero-positivity was fencing, with the highest exposure associated with deer from non-fenced hunting areas (OR: 2.21; 95% CI: 1.05-4.99). This study documented a widespread exposure to T. gondii in Danish cervids. Therefore the meat of the wild deer, in particular from roe deer and red deer, should be considered a significant risk of T. gondii infections to humans, if not properly cooked. Further, molecular studies to confirm the presence of infective parasitic stages in the muscles of deer used for consumption is recommended.
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BACKGROUND: In congenital hyperinsulinism (CHI), preoperative prediction of the histological subtype (focal, diffuse, or atypical) relies on genetics and 6-[18F]fluoro-l-3,4-dihydroxyphenylalanine (18F-DOPA) PET-CT. The scan also guides the localization of a potential focal lesion along with perioperative frozen sections. Intraoperative decision-making is still challenging. This study aimed to describe the characteristics and potential clinical impact of intraoperative ultrasound imaging (IOUS) during CHI surgery. METHODS: This was a prospective, observational study undertaken at an expert centre over a 2-year interval. IOUS was performed blinded to preoperative diagnostic test results (genetics and 18F-DOPA PET-CT), followed by unblinding and continued IOUS during pancreatic resection. Characteristics and clinical impact were assessed using predefined criteria. RESULTS: Eighteen consecutive, surgically treated patients with CHI, with a median age of 5.5 months, were included (focal 12, diffuse 3, atypical 3). Focal lesions presented as predominantly hypoechoic, oval lesions with demarcated or blurred margins. Patients with diffuse and atypical disease had varying echogenicity featuring stranding and non-shadowing hyperechoic foci in three of six, whereas these characteristics were absent from those with focal lesions. The blinded IOUS-based subclassification was correct in 17 of 18 patients; one diffuse lesion was misclassified as focal. IOUS had an impact on the surgical approach in most patients with focal lesions (9 of 12), and in those with diffuse (2 of 3) and atypical (2 of 3) disease when the resection site was close to the bile or pancreatic duct. CONCLUSION: Uniform IOUS characteristics made all focal lesions identifiable. IOUS had a clinical impact in 13 of 18 patients by being a useful real-time supplementary modality in terms of localizing focal lesions, reducing the need for frozen sections, and preserving healthy tissue and delicate structures.
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Hiperinsulinismo Congénito/diagnóstico por imagen , Hiperinsulinismo Congénito/cirugía , Páncreas/diagnóstico por imagen , Toma de Decisiones Clínicas , Hiperinsulinismo Congénito/patología , Femenino , Humanos , Lactante , Periodo Intraoperatorio , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Masculino , Páncreas/patología , Páncreas/cirugía , Estudios Prospectivos , Método Simple Ciego , UltrasonografíaRESUMEN
BACKGROUND: Most patients undergo follow-up after surgery for cancers of the gastro-oesophageal junction, stomach or pancreas, but data to support which modalities to use and the frequency of investigation are limited. METHODS: Patients in the EUFURO study were randomized to either visits to the outpatient clinic at 3, 6, 9, 12, 18, and 24 months after surgery (standard), or to the addition of [18F]fluorodeoxyglucose (FDG) PET-CT and endoscopic ultrasonography (EUS) with guided fine-needle aspiration biopsy to clinical assessments (intervention). Data from the intervention arm were used to analyse the diagnostic performance of endosonography or [18F]FDG PET-CT in detecting recurrences. RESULTS: During the scheduled follow-up, 42 of 89 patients developed recurrence; PET-CT and EUS in combination detected 38 of these recurrences. EUS detected 23 of the 42 patients with recurrent disease during follow-up and correctly diagnosed 17 of 19 locoregional recurrences. EUS was able to detect isolated locoregional recurrence in 11 of 13 patients. In five patients, EUS was false-positive for isolated locoregional recurrence owing to missed distant metastases. PET-CT detected locoregional recurrence in only 12 of 19 patients, and isolated locoregional recurrence in only 7 of 13. False-positive PET-CT results in 23 patients led to a total of 44 futile procedures. CONCLUSION: Accuracy in detecting recurrences by concomitant use of PET-CT and EUS was high (90 per cent). PET-CT had moderate to high sensitivity for overall recurrence detection, but low specificity. EUS was superior to PET-CT in the detection of locoregional and isolated locoregional recurrences.
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Endosonografía , Neoplasias Esofágicas/cirugía , Unión Esofagogástrica/cirugía , Recurrencia Local de Neoplasia/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias Gástricas/cirugía , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Anciano , Biopsia con Aguja Fina , Endosonografía/métodos , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/patología , Unión Esofagogástrica/diagnóstico por imagen , Unión Esofagogástrica/patología , Femenino , Fluorodesoxiglucosa F18 , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radiofármacos , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/patologíaRESUMEN
AIMS: To determine inactivation of Cryptosporidium parvum oocysts and reduction of Escherichia coli and enterococci in cattle slurry added aqueous ammonia. METHODS AND RESULTS: Escherichia coli, enterococci and nonviable C. parvum oocysts (DAPI+PI+) were enumerated every second day for 2 weeks in cattle slurry amended with 60 mmol l-1 aq. ammonia and compared with untreated slurry at three temperatures. Regardless of temperature, the proportion of nonviable C. parvum oocysts increased significantly faster over time in slurry with added ammonia than raw slurry (P = 0·021) corresponding to 62·0% higher inactivation (P = 0·001) at day 14. Additionally, 91·8% fewer E. coli and 27·3% fewer enterococci were observed in slurry added ammonia at day 14 compared to raw slurry. CONCLUSION: The addition of aqueous ammonia to raw slurry significantly reduced the viability of C. parvum oocysts and numbers of bacterial indicators. Hence, ammonia is usable at lower pathogen concentrations in slurry before application to agricultural land. SIGNIFICANCE AND IMPACT OF THE STUDY: Livestock waste is a valuable source of plant nutrients and organic matter, but may contain high concentrations of pathogens like E. coli and Cryptosporidium sp. that can be spread in the environment, and cause disease outbreaks. However, die-off rates of pathogens in organic waste can increase following increasing ammonia concentrations.
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Amoníaco/farmacología , Cryptosporidium parvum/efectos de los fármacos , Enterococcus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Oocistos/efectos de los fármacos , Animales , Bovinos , Supervivencia Celular , Dinamarca , Heces/microbiología , Heces/parasitología , Oocistos/aislamiento & purificación , TemperaturaRESUMEN
Understanding of the processes of petroleum source rock (SR) accumulation in lacustrine rift basins and the behavior of lake systems as long-term carbon sinks is fragmentary. Investigation of an 800 m thick (500 m core and ~ 300 m outcrop), deep-lacustrine, Oligocene section in Vietnam, provides a rare insight into the controls and deposition of organic carbon (OC) and SR formation in continental rift basins. A multidisciplinary dataset, combining elemental data, inorganic and organic geochemistry with sedimentology, shows that the richest alginite-prone, sapropelic SR developed during periods of relative tectonic quiescence characterized by moderate primary productivity in a mainly dysoxic lacustrine basin. Increased rift activity and further development of graben morphology intensified water column stratification and anoxia, which hindered nutrient recycling. Sapropelic organic matter (OM) continued to accumulate, but with increasing amorphous OM content and decreasing total OC values. Periods of increased seasonality were characterized by thermocline weakening, enhanced mixing of water columns, increased primary productivity and diatom blooming. The results suggest that a change from dysoxia towards anoxia or extreme primary productivity does not necessarily enhance OC burial and SR quality. External nutrient input from a phosphate-rich hinterland is sufficient for sapropel formation, whereas the main limiting factor is methanogenesis.
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From a longitudinal survey conducted on 30 Danish mink farms in 2016, 11.0% of faecal samples (456/4140) were positive for Cystoisospora laidlawi oocysts by microscopy, with 60% (189/315) of mink being positive at least once during the study period. Morphological analysis of sporulated oocysts identified Cystoisospora oocysts measuring 34.3 × 29.5 µm with an oocyst length/width (L/W) ratio of 1.2. The morphological features of the oocysts were identical to Isospora laidlawi previously morphological identified in farmed mink from Denmark and elsewhere. Phylogenetic analysis of 18S rDNA sequences (1221 bp) from three positive mink indicated that Cystoisospora from mink shared the highest genetic similarity to C. canis from a Canadian dog (99.6%). The phylogenetic analysis placed Cystoisospora from mink in a clade with other Cystoisospora isolates.
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Isospora/aislamiento & purificación , Isosporiasis/veterinaria , Visón/parasitología , Infecciones Protozoarias en Animales/parasitología , Animales , ADN Protozoario/genética , Dinamarca/epidemiología , Granjas , Heces/parasitología , Isospora/clasificación , Isospora/citología , Isospora/genética , Isosporiasis/parasitología , Oocistos/clasificación , Oocistos/citología , Oocistos/genética , Oocistos/aislamiento & purificación , Filogenia , ARN Ribosómico 18S/genéticaRESUMEN
INTRODUCTION: Inflammatory collateral cysts are uncommon cysts primarily affecting first permanent molars during their eruption. There are diagnostic challenges that can be overcome with CBCT imaging. However, given the paediatric age group for this condition, there are patient cooperation and radiation dose factors to consider when justifying the scan. The aim of this case series study is to illustrate the value of CBCT in imaging and diagnosing inflammatory collateral cysts in paediatric patients, to highlight the need for a multidisciplinary approach for this uncommon pathological condition and to review the relevant literature. CASE SERIES DESCRIPTION AND RESULTS: We present three patients aged between 6 and 11 years of age with inflammatory collateral cysts affecting their first or second permanent molars for which CBCT imaging was utilised. All patients underwent cyst enucleation with preservation or extraction of affected teeth under general anaesthesia. DISCUSSION: Inflammatory collateral cysts are likely to be under reported given their indistinct clinical features and radiological signs. Conventional planar radiographs may not reveal this lesions size and full extent. CBCT overcomes these limitations; however, careful assessment of patient cooperation is needed and a low-dose protocol should be used. CONCLUSIONS: CBCT can provide useful imaging information which is difficult to obtain using conventional radiography, especially in cases where an inflammatory collateral cyst is suspected.
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Quistes , Tomografía Computarizada de Haz Cónico Espiral , Niño , Tomografía Computarizada de Haz Cónico , Humanos , Diente Molar , Estudios RetrospectivosRESUMEN
Members of the crustacean subclass Copepoda are likely the most abundant metazoans worldwide. Pelagic marine species are critical in converting planktonic microalgae to animal biomass, supporting oceanic food webs. Despite their abundance and ecological importance, only six copepod genomes are publicly available, owing to a number of factors including large genome size, repetitiveness, GC-content, and small animal size. Here, we report the seventh representative copepod genome and the first genome and the first transcriptome from the calanoid copepod species Acartia tonsa Dana, which is among the most numerous mesozooplankton in boreal coastal and estuarine waters. The ecology, physiology, and behavior of A. tonsa have been studied extensively. The genetic resources contributed in this work will allow researchers to link experimental results to molecular mechanisms. From PCR-free whole genome sequence and mRNA Illumina data, we assemble the largest copepod genome to date. We estimate that A. tonsa has a total genome size of 2.5 Gb including repetitive elements we could not resolve. The nonrepetitive fraction of the genome assembly is estimated to be 566 Mb. Our DNA sequencing-based analyses suggest there is a 14-fold difference in genome size between the six members of Copepoda with available genomic information. This finding complements nucleus staining genome size estimations, where 100-fold difference has been reported within 70 species. We briefly analyze the repeat structure in the existing copepod whole genome sequence data sets. The information presented here confirms the evolution of genome size in Copepoda and expands the scope for evolutionary inferences in Copepoda by providing several levels of genetic information from a key planktonic crustacean species.
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Evolución Biológica , Copépodos/genética , Tamaño del Genoma , Animales , Genoma , TranscriptomaRESUMEN
OBJECTIVE: Maintaining upright posture is a complex task governed by the integration of afferent sensorimotor and visual information with compensatory neuromuscular reactions. The objective of the present work was to characterize the visual dependency and functional dynamics of cortical activation during postural control. APPROACH: Proprioceptic vibratory stimulation of calf muscles at 85 Hz was performed to evoke postural perturbation in open-eye (OE) and closed-eye (CE) experimental trials, with pseudorandom binary stimulation phases divided into four segments of 16 stimuli. 64-channel EEG was recorded at 512 Hz, with perturbation epochs defined using bipolar electrodes placed proximal to each vibrator. Power spectra variation and linearity analysis was performed via fast Fourier transformation into six frequency bands (Δ, 0.5-3.5 Hz; θ, 3.5-7.5 Hz; α, 7.5-12.5 Hz; ß, 12.5-30 Hz; [Formula: see text], 30-50 Hz; and [Formula: see text], 50-80 Hz). Finally, functional connectivity assessment was explored via network segregation and integration analyses. MAIN RESULTS: Spectra variation showed waveform and vision-dependent activation within cortical regions specific to both postural adaptation and habituation. Generalized spectral variation yielded significant shifts from low to high frequencies in CE adaptation trials, with overall activity suppressed in habituation; OE trials showed the opposite phenomenon, with both adaptation and habituation yielding increases in spectral power. Finally, our analysis of functional dynamics reveals novel cortical networks implicated in postural control using EEG source-space brain networks. In particular, our reported significant increase in local θ connectivity may signify the planning of corrective steps and/or the analysis of falling consequences, while α band network integration results reflect an inhibition of error detection within the cingulate cortex, likely due to habituation. SIGNIFICANCE: Our findings principally suggest that specific cortical waveforms are dependent upon the availability of visual feedback, and we furthermore present the first evidence that local and global brain networks undergo characteristic modification during postural control.
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Corteza Cerebral/fisiología , Habituación Psicofisiológica/fisiología , Red Nerviosa/fisiología , Equilibrio Postural/fisiología , Propiocepción/fisiología , Vibración , Adaptación Fisiológica/fisiología , Adulto , Electroencefalografía/métodos , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND: Copepods make up the largest zooplankton biomass in coastal areas and estuaries and are pivotal for the normal development of fish larva of countless species. During spring in neritic boreal waters, the copepod pelagic biomass increases rapidly from near absence during winter. In the calanoid species Acartia tonsa, a small fraction of eggs are dormant regardless of external conditions and this has been hypothesized to be crucial for sediment egg banks and for the rapid biomass increase during spring. Other eggs can enter a state of induced arrest called quiescence when external conditions are unfavourable. While temperature is known to be a pivotal factor in the transition from developing to resting eggs and back, the role of pH and free Oxygen in embryo development has not been systematically investigated. RESULTS: Here, we show in a laboratory setting that hypoxic conditions are necessary for resting eggs to maintain a near-intact rate of survival after several months of induced resting. We further investigate the influence of pH that is realistic for natural sediments on the viability of resting eggs and document the effect that eggs have on the pH of the surrounding environment. We find that resting eggs acidify their immediate surroundings and are able to survive in a wide range of pH. CONCLUSIONS: This is the first study to demonstrate the importance of hypoxia on the survival capabilities of A. tonsa resting eggs in a controlled laboratory setting, and the first to show that the large majority of quiescent eggs are able to tolerate prolonged resting. These findings have large implications for the understanding of the recruitment of copepods from sediment egg banks, which are considered the primary contributor of nauplii seeded to pelagic populations in nearshore habitats in late spring.
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Copépodos/crecimiento & desarrollo , Diapausa/fisiología , Anaerobiosis , Animales , Embrión no Mamífero/fisiología , Desarrollo Embrionario/fisiología , Óvulo/crecimiento & desarrolloRESUMEN
Essentials Factor (F)VIII with an intermediate-length B-domain showed higher levels in murine gene therapy. FVIII with different B-domain lengths were analysed. FVIII variants with B-domains between 186 and 240 amino acids (aa) have extended half-life in mice. Reduced cell binding of FVIII with a 237aa B-domain may explain the extended half-life. SUMMARY: Background Factor VIII consists of the A1-domain, A2-domain, B-domain, A3-domain, C1-domain, and C2-domain. FVIII with an intermediate-length B-domain of 226 amino acids (aa) has previously been evaluated in murine gene therapy studies. Objective To characterize FVIII with intermediate-length B-domains in vitro and in vivo in F8-knockout (KO) mice. Methods and results FVIII molecules with B-domains of 186-240aa had longer half-lives in F8-KO mice than FVIII molecules with shorter or longer B-domains. FVIII with a B-domain containing the 225 N-terminal aa fused to the 12 C-terminal aa of the wild-type B-domain (FVIII-237) had a 1.6-fold extended half-life in F8-KO mice as compared with FVIII with a 21aa B-domain (FVIII-21). The in vitro and in vivo activity of FVIII-237 were comparable to those of FVIII-21, as was binding to von Willebrand factor. Cell binding to LDL receptor-related protein 1 (LRP-1)-expressing cells was markedly reduced for FVIII-237 as compared with FVIII-21, whereas the affinity for LRP-1 was not reduced in surface plasmon resonance (SPR) studies. FVIII-21 cell binding and internalization could be inhibited by a fragment consisting of the 226 N-terminal aa of the FVIII B-domain, and SPR analysis suggested that this B-domain fragment might bind with weak affinity to FVIII-21. Conclusion Reduced cell binding of FVIII-237 might explain the observed extended half-life in F8-KO mice. This may contribute to the increased FVIII levels measured in murine gene therapy studies using FVIII constructs with similar B-domain lengths.
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Coagulantes/farmacocinética , Factor VIII/farmacocinética , Hemofilia A/tratamiento farmacológico , Animales , Línea Celular , Coagulantes/sangre , Modelos Animales de Enfermedad , Factor VIII/genética , Técnicas de Inactivación de Genes , Semivida , Hemofilia A/sangre , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Ratones Noqueados , Unión Proteica , Dominios Proteicos , Proteínas Recombinantes/farmacocinéticaRESUMEN
INTRODUCTION: The aim of this study was an analysis of the feasibility of a picosecond infrared laser fiber-assisted sclerostomy (PIRL-FAST) using a novel sapphire fiber and different energy levels of the picosecond laser. METHOD: The laser-assisted sclerostomy was carried out with a newly generated sapphire fiber of the PIRL-HP2-1064 OPA-3000 (Attodyne, Canada). Immediately after the intervention, the eyes were fixed in phosphate-buffered 3.5% formaldehyde. For subsequent histological analysis the eyes were cut into 4⯵m thick sections and stained with hematoxylin and eosin (H&E, Merck, Darmstadt, Germany). All preparations were then scanned and digitalized using the MIRAX SCAN (Carl Zeiss Microimaging GmbH, Jena, Germany). RESULTS: The pulse energies 150 µJ (Nâ¯= 4), 175 µJ (Nâ¯= 6), 200 µJ (Nâ¯= 7) and 250 µJ (Nâ¯= 6) were selected. Within the framework of this first feasibility analysis 400⯵m (10 sequential sections) of the sclerotomies were evaluated. The mean area of PIRL-FAST showed a dependency on the pulse energy applied. The diameter of the collateral damage zone (CDZ) depended on the pulse energy used. The largest CDZ could be measured using the highest pulse energy in this experiment (250⯵J). The environmental scanning electron microscope (ESEM) results revealed circular smooth sclerostomy wall with only minimal change of tissue ultrastructure. CONCLUSION: The PIRL-FAST using sapphire fibers is a new minimally invasive instrument to provide robust stenting from the anterior chamber to the subconjunctival space. Since the PIRL has proven to work efficiently in sectioning several tissues with minimal collateral damage these first proof of principle experiments might pave the way for a new minimally invasive glaucoma surgery strategy. We have already initiated experiments to analyze the wound healing and scar formation in vivo.
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Terapia por Láser , Esclerostomía , Cicatriz , Alemania , Humanos , Rayos LáserRESUMEN
A survey was conducted on 30 Danish mink farms from April to October 2016 to determine the prevalence and species of Eimeria in Danish farmed mink. In total, 2.6% of mink faecal samples (108/4140) were positive for Eimeria vison-like oocysts by microscopy, with 24.8% (78/315) of mink being positive at least once during the study period. Morphological analysis of sporulated oocysts (n = 20) identified Eimeria vison-like oocysts measuring 21.0 × 13.8 µm with a length/width (L/W) ratio of 1.5. Phylogenetic analysis of 18S rRNA sequences (1221 bp) from three positive mink indicated that Eimeria vison-like shared the highest genetic similarity to Eimeria sp. ex Apodemus agrarius from a Striped field mouse (A. agrarius) from the Czech Republic (99.6%). Analysis of a shorter region of 18S (531 bp) revealed that the E. vison-like genotype sequences grouped in the same clade and shared 97.7% similarity with E. furonis. At the cytochrome c oxidase subunit I (COI) locus, mink-derived sequences were not available from GenBank and phylogenetic analysis placed the novel E. vison-like in a clade with E. cf. ictidea (99.4% similarity) from a black footed ferret (Mustela nigripes) from Canada.
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Coccidiosis/epidemiología , Coccidiosis/veterinaria , Eimeria/clasificación , Visón/parasitología , Oocistos/fisiología , Animales , Coccidiosis/parasitología , Dinamarca/epidemiología , Eimeria/genética , Eimeria/aislamiento & purificación , Complejo IV de Transporte de Electrones/genética , Heces/parasitología , Ratones , Oocistos/clasificación , Oocistos/aislamiento & purificación , Filogenia , Reacción en Cadena de la Polimerasa/veterinaria , ARN Ribosómico 18S/genéticaRESUMEN
In Western Europe, the Echinococcus multilocularis lifecycle is predominantly sylvatic, typically involving red foxes (Vulpes vulpes) as the main definitive hosts with Microtus spp. and Arvicola spp. as intermediate hosts. During a 4-year surveillance study (2012-2015), Danish red foxes and raccoon dogs (n = 1345) were examined for E. multilocularis. Moreover, 134 insectivores and rodents collected in South Jutland during spring and summer 2016 were examined for the presence of metacestodes. The sedimentation and counting technique and molecular typing were used to identify E. multilocularis infections in the carnivores, while the rodent livers were examined macro- and microscopically for parasite lesions. Following morphological identification of E. multilocularis adult worms, the identity was verified by sequence analysis of the 12S rRNA gene in most cases (n = 13). Echinococcus multilocularis infection was demonstrated in 19 red foxes (Vulpes vulpes) originating from only two specific areas of South Jutland, namely Højer and Grindsted, and in two raccoon dogs (Nyctereutes procyonoides), originating from Højer. In Højer, 28.5% (CI 95% 11.7-45.3) of the examined red foxes were E. multilocularis positive per year. Moreover, positive red foxes were identified each year from 2012 to 2015, while E. multilocularis positive red foxes were only identified in Grindsted in 2013 (4.0%) and 2014 (6.4%). In contrast, all collected rodents were negative for E. multilocularis. We conclude that E. multilocularis is locally endemic in South Jutland with a high local prevalence in Højer.
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Arvicolinae/parasitología , Equinococosis/epidemiología , Equinococosis/veterinaria , Echinococcus multilocularis/aislamiento & purificación , Zorros/parasitología , Perros Mapache/parasitología , Animales , Dinamarca/epidemiología , Echinococcus multilocularis/clasificación , Echinococcus multilocularis/genética , Tipificación Molecular , Prevalencia , ARN Ribosómico/genéticaRESUMEN
Scholars from many different intellectual disciplines have attempted to measure, estimate, or quantify resilience. However, there is growing concern that lack of clarity on the operationalization of the concept will limit its application. In this paper, we discuss the theory, research development and quantitative approaches in ecological and community resilience. Upon noting the lack of methods that quantify the complexities of the linked human and natural aspects of community resilience, we identify several promising approaches within the ecological resilience tradition that may be useful in filling these gaps. Further, we discuss the challenges for consolidating these approaches into a more integrated perspective for managing social-ecological systems.
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Ecología , Ecosistema , HumanosRESUMEN
Essentials Activated FVII (FVIIa) and FX (FXa) are inhibited by tissue factor pathway inhibitor (TFPI). A monoclonal antibody, mAb2F22, was raised against the N-terminal fragment of TFPI (1-79). mAb2F22 bound exclusively to the K1 domain of TFPI (KD â¼1 nm) and not to the K2 domain. mAb2F22 interfered with inhibition of both FVIIa and FXa activities and restored clot formation. SUMMARY: Background Initiation of coagulation is induced by binding of activated factor VII (FVIIa) to tissue factor (TF) and activation of factor X (FX) in a process regulated by tissue factor pathway inhibitor (TFPI). TFPI contains three Kunitz-type protease inhibitor domains (K1-K3), of which K1 and K2 block the active sites of FVIIa and FXa, respectively. Objective To produce a monoclonal antibody (mAb) directed towards K1, to characterize the binding epitope, and to study its effect on TFPI inhibition. Methods A monoclonal antibody, mAb2F22, was raised against the N-terminal TFPI(1-79) fragment. Binding data were obtained by surface plasmon resonance analysis. The Fab-fragment of mAb2F22, Fab2F22, was expressed and the structure of its complex with TFPI(1-79) determined by X-ray crystallography. Effects of mAb2F22 on TFPI inhibition were measured in buffer- and plasma-based systems. Results mAb2F22 bound exclusively to K1 of TFPI (KD ~1 nm) and not to K2. The crystal structure of Fab2F22/TFPI (1-79) mapped an epitope on K1 including seven residues upstream of the domain. TFPI inhibition of TF/FVIIa amidolytic activity was neutralized by mAb2F22, although the binding epitope on K1 did not include the P1 residue. Binding of mAb2F22 to K1 blocked TFPI inhibition of the FXa amidolytic activity and normalized hemostasis in hemophilia human A-like plasma and whole blood. Conclusion mAb2F22 blocked TFPI inhibition of both FVIIa and FXa activities and mapped a FXa exosite for binding to K1. It reversed TFPI feedback inhibition of TF/FVIIa-induced coagulation and restored clot formation in FVIII-neutralized human plasma and blood.