Cat Model Research Articles

Construction of tissue-engineered human corneal endothelium for corneal endothelial regeneration using a crosslinked amniotic membrane scaffold

Descemet's membrane endothelial keratoplasty (DMEK) may provide fast visual rehabilitation in the therapy of corneal endothelial disorders. However, due to shortage of donated corneas, how to construct a corneal endothelial substitute with powerful functions that can be used for DMEK is still unsolved. Herein, we introduced the method of corneal crosslinking (CXL) and conjugated the components of native Descemet's membrane (DM) to improve the mechanical properties and the biocompatibility of denuded amniotic membrane (dAM), further assessed their effects on cell adhesion, proliferation, YAP translocation, and metabolic activity in human corneal endothelial (HCE) cells. Using modified crosslinked dAM (mcdAM) and non-transfected HCE cells, we constructed a tissue-engineered HCE (TE-HCE) and evaluated its functions in cat and monkey models as well. Our results showed that the mechanical properties of mcdAM were improved effectively by CXL, and the adhesion, proliferation, and YAP translocation of HCE cells were dose-dependently improved after ECM modification. The combination of 0.01 mg/mL laminin with 0.1 mg/mL fibronectin showed the highest efficacy. Then, the TE-HCE was constructed in vitro, with a high density of 3612 ± 243 cells/mm2. Results of DMEK in animal models showed that corneal transparency was maintained, accompanied with normal morphology and histological structure of the regenerated corneal endothelium. Therefore, CXL combined with DM-mimic-coating methods could effectively improve the mechanical properties of dAM and enhance the biocompatibility with HCE cells. The constructed TE-HCE had normal histological structure and functioned well in animal models via DMEK, which could be used as a promising powerful equivalent of HCE. Statement of significanceUsing high-quality corneal endothelium and an appropriate endothelial keratoplasty is the most effective way for the treatment of corneal endotheliopathy. Descemet's membrane endothelial keratoplasty (DMEK) which can provide better visual acuity, lower immunological rejection rates, and improved graft survival is an ideal surgery at present. However, due to the shortage of donated corneas, it is urgent to find an equivalent substitute of corneal endothelial donor which is suitable for the DMEK surgery to solve the problem of corneal endothelial regeneration. Herein, we introduced the clinical cornea-crosslinking and Descemet's membrane-mimic-coating methods to build the modified crosslinked denuded amniotic membrane scaffold and further constructed a high-quality corneal endothelial functional substitute that can be used in DMEK surgery.

Heat stress and sperm production in the domestic cat

This study aimed to assess 1) the effect of high environmental temperatures on sperm production and 2) the effectiveness of a temperature-humidity index (THI) to predict the degree of thermal stress in a cat model. Semen collection was performed by electroejaculation for 18 mo in 20 tomcats maintained under controlled photoperiod. Still, temperature and humidity were not experimentally manipulated to describe the effect of natural climate conditions on seminal samples. Ejaculates (n = 512) were then grouped according to temperature records of the sampling day and compared by temperature and THI index. Significant lower sperm parameters and increase sperm tail abnormalities were observed during warm environments (temperature and THI). Concentration and total sperm count were the most affected parameters. Environmental temperatures of 28.5 °C with 54% relative humidity (THI = 77.07) and 27.9 °C with 66% humidity (THI = 77.84) were upper thresholds of moderate thermal stress. Moreover, days with relative humidity near 90% led to severe thermal stress with temperatures as low as 26.6 °C (THI = 78.88). The current study demonstrates the detrimental effect of high environmental temperatures on sperm quality in the domestic cat. This effect is observed at lower temperatures when high relative humidity is present. In this sense, the THI was a reliable predictor of the magnitude of thermal stress experienced by cats. Thus, cats from reproductive programs should be maintained under controlled photoperiod cycles with temperatures around 20 °C and humidity around 70% to avoid semen detrimental effects.

Selective augmentation of corticospinal motor drive with trans-spinal direct current stimulation in the cat

BackgroundA key outcome for spinal cord stimulation for neurorehabilitation after injury is to strengthen corticospinal system control of the arm and hand. Non-invasive, compared with invasive, spinal stimulation minimizes risk but depends on muscle-specific actions for restorative functions. ObjectiveWe developed a large-animal (cat) model, combining computational and experimental techniques, to characterize neuromodulation with transcutaneous spinal direct current stimulation (tsDCS) for facilitation of corticospinal motor drive to specific forelimb muscles. MethodsAcute modulation of corticospinal function by tsDCS was measured using motor cortex-evoked muscle potentials (MEPs). The effects of current intensity, polarity (cathodal, anodal), and electrode position on specific forelimb muscle (biceps vs extensor carpi radialis, ECR) MEP modulation were examined. Locations of a key target, the motoneuron pools, were determined using neuronal tracing. A high-resolution anatomical (MRI and CT) model was developed for computational simulation of spinal current flow during tsDCS. ResultsEffects of tsDCS on corticospinal excitability were robust and immediate, therefore supporting MEPs as a sensitive marker of tsDCS targeting. Varying cathodal/anodal current intensity modulated MEP enhancement/suppression, with higher cathodal sensitivity. Muscle-specificity depended on cathode position; the rostral position preferentially augmented biceps responses and the caudal position, ECR responses. Precise anatomical current-flow modeling, supplemented with target motor pool distributions, can explain tsDCS focality on muscle groups. ConclusionAnatomical current-flow modeling with physiological validation based on MEPs provides a framework to optimize muscle-specific tsDCS interventions. tsDCS targeting of representative motor pools enables muscle- and response-specific neuromodulation of corticospinal motor drive.

Toward Assessing the Functional Connectivity of Spinal Neurons.

Spinal interneurons play a critical role in motor output. A given interneuron may receive convergent input from several different sensory modalities and descending centers and relay this information to just as many targets. Therefore, there is a critical need to quantify populations of spinal interneurons simultaneously. Here, we quantify the functional connectivity of spinal neurons through the concurrent recording of populations of lumbar interneurons and hindlimb motor units in the in vivo cat model during activation of either the ipsilateral sural nerve or contralateral tibial nerve. Two microelectrode arrays were placed into lamina VII, one at L3 and a second at L6/7, while an electrode array was placed on the surface of the exposed muscle. Stimulation of tibial and sural nerves elicited similar changes in the discharge rate of both interneurons and motor units. However, these same neurons showed highly significant differences in prevalence and magnitude of correlated activity underlying these two forms of afferent drive. Activation of the ipsilateral sural nerve resulted in highly correlated activity, particularly at the caudal array. In contrast, the contralateral tibial nerve resulted in less, but more widespread correlated activity at both arrays. These data suggest that the ipsilateral sural nerve has dense projections onto caudal lumbar spinal neurons, while contralateral tibial nerve has a sparse pattern of projections.

Effects of chronic implantation and long-term stimulation of a cochlear implant in the partial hearing cat model

The expansion of criteria for cochlear implantation has resulted in increasing numbers of cochlear implant subjects having some level of residual hearing. The present study examined the effects of implantation surgery and long-term electrical stimulation on residual hearing in a partially deafened cat model. Eighteen animals were partially deafened, implanted and chronically stimulated. Implantation resulted in a pronounced loss evident 2-weeks post implantation of up to 30–40 dB at 4 & 8 kHz which was statistically significant (2-way RM ANOVA (Time, Frequency): p(Time) = 0.001; p(Frequency) < 0.001; p(Time x Frequency) < 0.001)). Chronic stimulation resulted in a significant (RM ANOVA: p(Time) = 0.030) ongoing hearing loss, with 5 animals (∼30%) exhibiting an increase in threshold of 20 dB or more. Different loss profiles were evident with peripheral and central hearing assessments suggests that changes in ‘central gain’ may be occurring. Despite significant loss of hair cells and spiral ganglion neurons and distinct fibrous tissue growth in the scala tympani following implantation and long-term electrical stimulation, there were no significant correlations with any histological measures and ongoing hearing loss. The partially deafened, chronically stimulated cat model provides a clinically relevant model in which to further investigate the cause of the delayed hearing loss following cochlear implant surgery and use.

Modelling Fire Risk Exposure for France Using Machine Learning

Wildfires generating damage to assets are extremely rare in France. The peril is not covered by the French natural catastrophes insurance scheme (law of 13 July 1982). In the context of the changing climate, Caisse Centrale de Réassurance—the French state-owned reinsurance company involved in the Nat Cat insurance scheme—decided to develop its knowledge on the national exposure of France to wildfire risks. Current and future forest fires events have to be anticipated in case one of the events threatens buildings. The present work introduces the development of a catastrophe loss risk model (Cat model) for forest fires for the French metropolitan area. Cat models are the tools used by the (re)insurance sector to assess their portfolios’ exposure to natural disasters. The open-source national Promethée database focusing on the South of France for the period 1973–2019 was used as training data for the development of the hazard unit using machine learning-based methods. As a result, we observed an extension of the exposure to wildfire in northern areas, namely Landes, Pays-de-la-Loire, and Bretagne, under the RCP 4.5 scenario. The work highlighted the need to understand the multi-peril exposure of the French country and the related economic damage. This is the first study of this kind performed by a reinsurance company in collaboration with a scholarly institute, in this case EURIA Brest.

Subdural neural interfaces for long-term electrical recording, optical microscopy and magnetic resonance imaging

Though commonly used, metal electrodes are incompatible with brain tissues, often leading to injury and failure to achieve long-term implantation. Here we report a subdural neural interface of hydrogel functioning as an ionic conductor, and elastomer as a dielectric. We demonstrate that it incurs a far less glial reaction and less cerebrovascular destruction than a metal electrode. Using a cat model, the hydrogel electrode was able to record electrical signals comparably in quality to a metal electrode. The hydrogel-elastomer neural interface also readily facilitated multimodal functions. Both the hydrogel and elastomer are transparent, enabling in vivo optical microscopy. For imaging, cerebral vessels and calcium signals were imaged using two-photon microscopy. The new electrode is compatible with magnetic resonance imaging and does not cause artifact images. Such a new multimodal neural interface could represent immediate opportunity for use in broad areas of application in neuroscience research and clinical neurology.

A domestic cat (Felis silvestris catus) model of triarchic psychopathy factors: Development and initial validation of the CAT-Tri+ questionnaire

We operationalised the triarchic model of psychopathy (boldness, meanness, and disinhibition) in domestic cats using a cat triarchic (CAT-Tri) questionnaire. In study 1 (n = 549), we identified candidate items for CAT-Tri scales using thematically analysed cat owner questionnaire responses. In study 2 (n = 1463), owners completed a questionnaire battery; the preliminary CAT-Tri questionnaire, Feline Five, and Cat-Owner Relationship Subscales. In study 3 (n = 30), associations between feline daily activity and Cat-Tri scales were investigated. A five-factor cat triarchic plus (CAT-Tri+) solution emerged: boldness, disinhibition, meanness, pet-unfriendliness, and human-unfriendliness. Disinhibition and pet-unfriendliness predicted a higher quality cat-owner relationship; meanness and boldness predicted a lower quality relationship. Findings provide insight into the structure of triarchic psychopathy in cats.

Cloudburst-disaster modelling. A new open-source catastrophe model

Cloudburst flash floods cause big casualties and economic losses. This study primarily investigated if a cloudburst catastrophe (cat) model could be constructed to meaningfully assess such a hazard, exposure and vulnerability in Swedish urban context. Rainfall intensity was used directly as hazard measure, bypassing hydraulic water-level modelling, to predict vulnerability. The Splash (Swedish pluvial modelling analysis and safety handling) cloudburst-disaster model was constructed using the Oasis Loss Modelling Framework, and was based on individual property values and building locations, property-level insurance-loss data, high-resolution geographical data, and rainfall data from a dense municipal gauge network in the city of Jönköping. One major cloudburst event was used to derive a vulnerability curve. The following two events were used for validation and supported the hypothesis that the vulnerability curve changed with time because of municipal flood-risk-reduction measures after the first event. A faulty rain gauge during the first event, replaced by a trustworthy private gauge, clarified the very high sensitivity to cloudburst input. Given the limited amount of loss data, our results were uncertain but they pointed towards possible ways to further this study with other loss data at other locations, possibly using more easily available aggregated loss data. We concluded that a cat model based only on rainfall intensity provided acceptable results, thus providing an opening for future, simplified cloudburst cat models applicable in most geographical contexts where reliable cloudburst data are available, especially in cities with limited topographic data and hydraulic-modelling capacity.

Describing acid-base balance using three different methods of analysis in a feline acute haemorrhage-resuscitation model

ObjectiveTo describe acid-base status using the Henderson-Hasselbalch, Stewart and semi-quantitative methods of analysis in a feline haemorrhage-resuscitation model. Study designRandomized crossover study. AnimalsA total of six domestic cats (mean age, 21 months; weight, 4.9 kg). MethodsVenous blood samples were taken before haemorrhage, after haemorrhage at 30 minute intervals during fluid resuscitation and at 24 hours. The cats were anaesthetized and underwent following treatments: no purposeful haemorrhage and resuscitation (NoPHR), purposeful haemorrhage followed by either lactated Ringer’s solution (LRS) or 6% tetrastarch 130/0.4 (Voluven) for resuscitation. LRS and Voluven were administered at 60 and 20 mL kg–1 hour–1, respectively, for 120 minutes. Variables used for the analysis methods were measured or calculated from the blood samples and then compared among treatments over time using a general linear mixed model (p < 0.05; data reported as mean and standard deviation). ResultsThe total blood loss at 120 minutes was 10.2 ± 2.3, 29.3 ± 9.0 and 29.1 ± 6.3 mL kg–1 for NoPHR, LRS and Voluven, respectively. Total volumes of LRS and Voluven administered were 120 and 40 mL kg–1, respectively. All cats became acidaemic during anaesthesia regardless of treatment. The Henderson-Hasselbalch method indicated that anaesthetized cats undergoing severe haemorrhage and resuscitation manifest a mixed acidosis. The Stewart method indicated two counter metabolic processes that contributed to the overall pH—decrease in apparent strong ion difference (acidosis) and decrease in total weak acids (alkalosis). The semi-quantitative method identified the free water and chloride effects as variables causing acidosis and the albumin effect causing alkalosis. Conclusions and clinical relevanceIn an experimental haemorrhage and resuscitation model in cats, blood pH was similar among treatments over time regardless of severe haemorrhage and resuscitation with LRS or Voluven or mild haemorrhage and no resuscitation.

A large animal model of RDH5-associated retinopathy recapitulates important features of the human phenotype.

Pathogenic variants in retinol dehydrogenase 5 (RDH5) attenuate supply of 11-cis-retinal to photoreceptors leading to a range of clinical phenotypes including night blindness because of markedly slowed rod dark adaptation and in some patients, macular atrophy. Current animal models (such as Rdh5-/- mice) fail to recapitulate the functional or degenerative phenotype. Addressing this need for a relevant animal model we present a new domestic cat model with a loss-of-function missense mutation in RDH5 (c.542G > T; p.Gly181Val). As with patients, affected cats have a marked delay in recovery of dark adaptation. In addition, the cats develop a degeneration of the area centralis (equivalent to the human macula). This recapitulates the development of macular atrophy that is reported in a subset of patients with RDH5 mutations and is shown in this paper in seven patients with biallelic RDH5 mutations. There is notable variability in the age at onset of the area centralis changes in the cat, with most developing changes as juveniles but some not showing changes over the first few years of age. There is similar variability in development of macular atrophy in patients and while age is a risk factor, it is hypothesized that genetic modifying loci influence disease severity, and we suspect the same is true in the cat model. This novel cat model provides opportunities to improve molecular understanding of macular atrophy and test therapeutic interventions for RDH5-associated retinopathies.

The scope for adaptive capacity in emergency departments: modelling performance constraints using control task analysis and social organisational cooperation analysis

Patient flow between the emergency department (ED) and hospital wards becomes problematic when bed availability is limited. To better understand the constraints that shape patient flow and everyday work in the ED, we applied Control Task Analysis (i.e. Contextual Activities Template, CAT) and Social Organisational Cooperation Analysis (SOCA) phases from the Cognitive Work Analysis framework to identify ways in which to optimise patient flow. The model and analysis were created through observations in the ED of clinicians (e.g. nurses, doctors), and professional staff (e.g. ward personnel, clerks). The CAT and SOCA-CAT models illustrate workspaces, patient journey phases, and patient volume within the department that are heavily loaded with tasks and human and non-human agents performing these tasks, while others are underutilised. The findings suggest that an ED’s adaptive capacity could be strengthened through the integration of additional human and non-human agents allowing the redistribution of clinical and non-clinical tasks. Practitioner Summary: Workflow in EDs is constrained by uneven geographical distribution of activities, insufficient adaptive support during critical patient journey phases and periods of high patient volume. Adaptive capacity could be strengthened by additional human and non-human agents in combination with a redistribution of tasks, supporting seamless successful structural and behavioural adaptation in ED.

Age estimation using methylation-sensitive high-resolution melting (MS-HRM) in both healthy felines and those with chronic kidney disease

Age is an important ecological tool in wildlife conservation. However, it is difficult to estimate in most animals, including felines—most of whom are endangered. Here, we developed the first DNA methylation-based age-estimation technique—as an alternative to current age-estimation methods—for two feline species that share a relatively long genetic distance with each other: domestic cat (Felis catus; 79 blood samples) and an endangered Panthera, the snow leopard (Panthera uncia; 11 blood samples). We measured the methylation rates of two gene regions using methylation-sensitive high-resolution melting (MS-HRM). Domestic cat age was estimated with a mean absolute deviation (MAD) of 3.83 years. Health conditions influenced accuracy of the model. Specifically, the models built on cats with chronic kidney disease (CKD) had lower accuracy than those built on healthy cats. The snow leopard-specific model (i.e. the model that resets the model settings for snow leopards) had a better accuracy (MAD = 2.10 years) than that obtained on using the domestic cat model directly. This implies that our markers could be utilised across species, although changing the model settings when targeting different species could lead to better estimation accuracy. The snow leopard-specific model also successfully distinguished between sexually immature and mature individuals.

Recursive Partitioning vs Computerized Adaptive Testing to Reduce the Burden of Health Assessments in Cleft Lip and/or Palate: Comparative Simulation Study.

BackgroundComputerized adaptive testing (CAT) has been shown to deliver short, accurate, and personalized versions of the CLEFT-Q patient-reported outcome measure for children and young adults born with a cleft lip and/or palate. Decision trees may integrate clinician-reported data (eg, age, gender, cleft type, and planned treatments) to make these assessments even shorter and more accurate.ObjectiveWe aimed to create decision tree models incorporating clinician-reported data into adaptive CLEFT-Q assessments and compare their accuracy to traditional CAT models.MethodsWe used relevant clinician-reported data and patient-reported item responses from the CLEFT-Q field test to train and test decision tree models using recursive partitioning. We compared the prediction accuracy of decision trees to CAT assessments of similar length. Participant scores from the full-length questionnaire were used as ground truth. Accuracy was assessed through Pearson’s correlation coefficient of predicted and ground truth scores, mean absolute error, root mean squared error, and a two-tailed Wilcoxon signed-rank test comparing squared error.ResultsDecision trees demonstrated poorer accuracy than CAT comparators and generally made data splits based on item responses rather than clinician-reported data.ConclusionsWhen predicting CLEFT-Q scores, individual item responses are generally more informative than clinician-reported data. Decision trees that make binary splits are at risk of underfitting polytomous patient-reported outcome measure data and demonstrated poorer performance than CATs in this study.

Applying Bayesian Optimization for Machine Learning Models in Predicting the Surface Roughness in Single-Point Diamond Turning Polycarbonate

This paper deals with the prediction of surface roughness in manufacturing polycarbonate (PC) by applying Bayesian optimization for machine learning models. The input variables of ultraprecision turning—namely, feed rate, depth of cut, spindle speed, and vibration of the X-, Y-, and Z-axis—are the main factors affecting surface quality. In this research, six machine learning- (ML-) based models—artificial neural network (ANN), Cat Boost Regression (CAT), Support Vector Machine (SVR), Gradient Boosting Regression (GBR), Decision Tree Regression (DTR), and Extreme Gradient Boosting Regression (XGB)—were applied to predict the surface roughness (Ra). The predictive performance of the baseline models was quantitatively assessed through error metrics: root means square error (RMSE), mean absolute error (MAE), and coefficient of determination (R2). The overall results indicate that the XGB and CAT models predict Ra with the greatest accuracy. In improving baseline models such as XGB and CAT, the Bayesian optimization (BO) is next used to determine their best hyperparameters, and the results indicate that XGB is the best model according to the evaluation metrics. Results have shown that the performance of the models has been improved significantly with BO. For example, the values of RMSE and MAE of XGB have decreased from 0.0076 to 0.0047 and from 0.0063 to 0.0027, respectively, for the training dataset. Using the testing dataset, the values of RMSE and MAE of XGB have decreased from 0.4033 to 0.2512 and from 0.2845 to 0.2225, respectively. Moreover, the vibrations of the X, Y, and Z axes and feed rate are the most significant feature in predicting the results, which is in high accordance with the literature. We find that, in a specified value domain, the vibration of the axes has a greater influence on the surface quality than does the cutting condition.

Rooting the Animal Tree of Life.

Identifying our most distant animal relatives has emerged as one of the most challenging problems in phylogenetics. This debate has major implications for our understanding of the origin of multicellular animals and of the earliest events in animal evolution, including the origin of the nervous system. Some analyses identify sponges as our most distant animal relatives (Porifera-sister hypothesis), and others identify comb jellies (Ctenophora-sister hypothesis). These analyses vary in many respects, making it difficult to interpret previous tests of these hypotheses. To gain insight into why different studies yield different results, an important next step in the ongoing debate, we systematically test these hypotheses by synthesizing 15 previous phylogenomic studies and performing new standardized analyses under consistent conditions with additional models. We find that Ctenophora-sister is recovered across the full range of examined conditions, and Porifera-sister is recovered in some analyses under narrow conditions when most outgroups are excluded and site-heterogeneous CAT models are used. We additionally find that the number of categories in site-heterogeneous models is sufficient to explain the Porifera-sister results. Furthermore, our cross-validation analyses show CAT models that recover Porifera-sister have hundreds of additional categories and fail to fit significantly better than site-heterogenuous models with far fewer categories. Systematic and standardized testing of diverse phylogenetic models suggests that we should be skeptical of Porifera-sister results both because they are recovered under such narrow conditions and because the models in these conditions fit the data no better than other models that recover Ctenophora-sister.

Exposure to epididymal extracellular vesicles enhances immature sperm function and sustains vitality of cryopreserved spermatozoa in the domestic cat model.

Extracellular vesicles (EVs) secreted by the epididymal epithelium transfer key factors to maturing spermatozoa. Using an in vitro system previously developed in our laboratory, the objective was to (1) characterize the impact of EV exposure on the fertilizing ability and developmental potential of immature sperm cells from the caput epididymidis and (2) examine the benefit of EV exposure to restore vitality of mature spermatozoa from the cauda epididymidis after freezing-thawing. EVs were isolated from entire epididymides and collected into pellets via ultracentrifugation. Immature spermatozoa from adult cats were isolated from the caput epididymis and incubated with EVs prior to in vitro fertilization. Similarly, mature spermatozoa were isolated from the cauda segment and cryopreserved prior to EV exposure and subsequent analysis of motility and developmental potential after fertilization. EV exposure did not affect the percentage of caput sperm penetration; however, it improved the fertilizing ability (faster pronuclear apposition) and the developmental potential (higher proportions of morula-blastocysts) of those immature sperm cells. While EV exposure was beneficial to the frozen-thawed sperm motility, it did not significantly improve the fertilizing ability and the developmental potential. Epididymal EVs contain multiple factors contributing to immature sperm function, specifically enhancing the ability to complete a faster pronuclear apposition with subsequently improved early embryonic development. Supplementation was also beneficial to the motility of spermatozoa that had undergone cryopreservation. Those new findings could lead to new options for male fertility treatment in animal models and humans.

Oocyte Meiotic Competence in the Domestic Cat Model: Novel Roles for Nuclear Proteins BRD2 and NPM1.

To participate in fertilization and embryo development, oocytes stored within the mammalian female ovary must resume meiosis as they are arrested in meiotic prophase I. This ability to resume meiosis, known as meiotic competence, requires the tight regulation of cellular metabolism and chromatin configuration. Previously, we identified nuclear proteins associated with the transition from the pre-antral to the antral follicular stage, the time at which oocytes gain meiotic competence. In this study, the objective was to specifically investigate three candidate nuclear factors: bromodomain containing protein 2 (BRD2), nucleophosmin 1 (NPM1), and asparaginase-like 1 (ASRGL1). Although these three factors have been implicated with folliculogenesis or reproductive pathologies, their requirement during oocyte maturation is unproven in any system. Experiments were conducted using different stages of oocytes isolated from adult cat ovaries. The presence of candidate factors in developing oocytes was confirmed by immunostaining. While BRD2 and ASRGL1 protein increased between pre-antral and the antral stages, changes in NPM1 protein levels between stages were not observed. Using protein inhibition experiments, we found that most BRD2 or NPM1-inhibited oocytes were incapable of participating in fertilization or embryo development. Further exploration revealed that inhibition of BRD2 and NPM-1 in cumulus-oocyte-complexes prevented oocytes from maturing to the metaphase II stage. Rather, they remained at the germinal vesicle stage or arrested shortly after meiotic resumption. We therefore have identified novel factors playing critical roles in domestic cat oocyte meiotic competence. The identification of these factors will contribute to improvement of domestic cat assisted reproduction and could serve as biomarkers of meiotically competent oocytes in other species.

Provision of interaural time difference information in chronic intracochlear electrical stimulation enhances neural sensitivity to these differences in neonatally deafened cats

Although performance with bilateral cochlear implants is superior to that with a unilateral implant, bilateral implantees have poor performance in sound localisation and in speech discrimination in noise compared to normal hearing subjects. Studies of the neural processing of interaural time differences (ITDs) in the inferior colliculus (IC) of long-term deaf animals, show substantial degradation compared to that in normal hearing animals. It is not known whether this degradation can be ameliorated by chronic cochlear electrical stimulation, but such amelioration is unlikely to be achieved using current clinical speech processors and cochlear implants, which do not provide good ITD cues. We therefore developed a custom sound processor to deliver salient ITDs for chronic bilateral intra-cochlear electrical stimulation in a cat model of neonatal deafness, to determine if long-term exposure to salient ITDs would prevent degradation of ITD processing. We compared the sensitivity to ITDs in cochlear electrical stimuli of neurons in the IC of cats chronically stimulated with our custom ITD-aware sound processor with sensitivity in acutely deafened cats with normal hearing development and in cats chronically stimulated with a clinical stimulator and sound processor. Animals that experienced stimulation with our custom ITD-aware sound processor had significantly higher neural sensitivity to ITDs than those that received stimulation from clinical sound processors. There was no significant difference between animals received no stimulation and those that received stimulation from clinical sound processors, consistent with findings from clinical cochlear implant users. This result suggests that development and use of clinical ITD-aware sound processing strategies from a young age may promote ITD sensitivity in the clinical population.

Vaccine Development for Severe Fever with Thrombocytopenia Syndrome.

Severe fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), is a tick-borne emerging zoonosis with a high case-fatality rate. At present, there is no approved SFTS vaccine, although the development of a vaccine would be one of the best strategies for preventing SFTS. This article focused on studies aimed at establishing small animal models of SFTS that are indispensable for evaluating vaccine candidates, developing these vaccine candidates, and establishing more practical animal models for evaluation. Innate immune-deficient mouse models, a hamster model, an immunocompetent ferret model and a cat model have been developed for SFTS. Several vaccine candidates for SFTS have been developed, and their efficacy has been confirmed using these animal models. The candidates consist of live-attenuated virus-based, viral vector-based, or DNA-based vaccines. SFTS vaccines are expected to be used for humans and companion dogs and cats. Hence for practical use, the vaccine candidates should be evaluated for efficacy using not only nonhuman primates but also dogs and cats. There is no practical nonhuman primate model of SFTS; however, the cat model is available to evaluate the efficacy of these candidate SFTS vaccines on domesticated animals.