Experimental studies in animals have shown that exposure to general anaesthesia in infancy can cause loss of cells in the central nervous system and long-term impairments in neurocognitive function. ...Some human epidemiological studies have shown increased risk of learning disability after repeated anaesthesia exposure in early childhood. Thus, we investigated in a highly translational rhesus monkey model, whether repeated exposure in infancy to the inhalation anaesthetic sevoflurane is associated with impaired visual recognition memory during the first two yr of life.
Rhesus monkeys of both sexes were exposed to sevoflurane inhalation anaesthesia on approximately postnatal day 7 and then again 14 and 28 days later, for four h each time. Visual recognition memory was tested using the visual paired comparison task, which measures memory by assessing preference for looking at a new image over a previously-viewed image. Monkeys were tested at 6–10 months of age, again at 12–18 months of age, and again at 24–30 months of age.
No memory impairment was detected at 6–10 months old, but significant impairment (reduced time looking at the novel image) was observed at 12–18 and 24–30 months old.
Repeated exposure of infant rhesus monkeys to sevoflurane results in visual recognition memory impairment that emerges after the first yr of life. This is consistent with epidemiological studies that show increased risk of learning disability after repeated exposure to anaesthesia in infancy/early childhood. Moreover, these deficits may emerge at later developmental stages, even when memory performance is unaffected earlier in development.
The global poultry industry has been faced with emerging broiler breast meat quality issues including conditions known as white striping (WS, white striations parallel to muscle fibers) and woody ...breast (WB, hardness of raw fillet). Experiments were conducted to evaluate effects of WS and WB hardness on meat quality traits in broiler breast fillets. In Exp. 1, birds were processed at approximately 9 wk of age and deboned at 4 h postmortem (PM); in Exp. 2, birds were processed at approximately 6 and 9 wk of age and deboned at 2 h PM. Fillets were categorized as: normal for both white striping and woody breast (NORM); moderate for white striping and mild for woody breast (MILD); severe for white striping and mild for woody breast (WS); severe for woody breast and moderate for white striping (WB); or severe for both white striping and woody breast (BOTH). Sarcomere length, gravimetric fragmentation index, marination uptake, cook loss, and Meullenet-Owens razor shear energy (MORSE) values on non-marinated and marinated fillets were assessed. Sarcomeres tended to be longer (P = 0.07) with increasing severity of WS and WB in both experiments and gravimetric fragmentation index did not differ (P > 0.05) among categories. Marinade uptake decreased (P < 0.05) with increasing severity of WS and WB. Cook losses of non-marinated and marinated fillets were greatest (P < 0.05) in the BOTH category. Even though MORSE values did not differ (P > 0.05) in non-marinated fillets, the marinated BOTH fillets had greater MORSE values (P < 0.05) than other categories of fillets in Exp. 1. Non-marinated NORM fillets had greater (P < 0.05) MORSE values than the other categories at 6 wk age; however, MORSE values did not differ (P > 0.05) among categories of marinated breasts. At 9 wk, WS and BOTH were higher (P < 0.05) in MORSE compared to NORM for non-marinated fillets, but similar to NORM marinated fillets. Results suggest that severe degrees of white striping and woody breast, individually or in combination, negatively impact meat quality, especially water holding capacity attributes such as marinade uptake and cook loss.
We have developed a portable and easily configurable genome annotation pipeline called MAKER. Its purpose is to allow investigators to independently annotate eukaryotic genomes and create genome ...databases. MAKER identifies repeats, aligns ESTs and proteins to a genome, produces ab initio gene predictions, and automatically synthesizes these data into gene annotations having evidence-based quality indices. MAKER is also easily trainable: Outputs of preliminary runs are used to automatically retrain its gene-prediction algorithm, producing higher-quality gene-models on subsequent runs. MAKER's inputs are minimal, and its outputs can be used to create a GMOD database. Its outputs can also be viewed in the Apollo Genome browser; this feature of MAKER provides an easy means to annotate, view, and edit individual contigs and BACs without the overhead of a database. As proof of principle, we have used MAKER to annotate the genome of the planarian Schmidtea mediterranea and to create a new genome database, SmedGD. We have also compared MAKER's performance to other published annotation pipelines. Our results demonstrate that MAKER provides a simple and effective means to convert a genome sequence into a community-accessible genome database. MAKER should prove especially useful for emerging model organism genome projects for which extensive bioinformatics resources may not be readily available.
Socio-emotional development is the expression and management of emotions, which in non-human primates can be examined using responses toward increasing levels of threat. Damage to the limbic system ...alters socio-emotional development in primates. Thus, neuronal and glial cell loss caused by exposure to general anaesthesia early in infancy might also impact socio-emotional development. We recently reported that repeated sevoflurane exposure in the first month of life alters emotional behaviours at 6 months of age and impairs visual recognition memory after the first year of life in rhesus monkeys. The present study evaluated socio-emotional behaviour at 1 and 2 yr of age in those same monkeys to determine the persistence of altered emotional behaviour.
Rhesus monkeys of both sexes were exposed to sevoflurane anaesthesia three times for 4 h each time in the first 6 weeks of life. At 1 and 2 yr of age, they were tested on the human intruder task, a well-established mild acute social stressor.
Monkeys exposed to sevoflurane as infants exhibited normal fear and hostile responses, but exaggerated self-directed (displacement) behaviours, a general indicator of stress and anxiety in non-human primates.
Early repeated sevoflurane exposure in infant non-human primates results in an anxious phenotype that was first detected at 6 months, and persists for at least 2 yr of age. This is the first demonstration of such a prolonged impact of early anaesthesia exposure on emotional reactivity.
Synthesis of TiO2 anatase nanocrystals by hydrothermal methods often results in the formation of small quantities of brookite, which is difficult to eliminate by tuning the reaction conditions and is ...usually present in the final nanomaterial. The effect of this impurity on the Raman spectrum in anatase nanomaterials has not been fully explored. In this work, a study on the effect of reaction temperature on the position and line shape of the low-wavenumber Raman peak is presented. A comparison of the spectra of nanomaterials of pure anatase and anatase with brookite impurity (4–13 nm), synthesized by hydrothermal microwave heating, is made. It is shown that the low-wavenumber Raman peak (100–300 cm–1) for pure anatase nanocrystals is strongly dependent on the nanocrystal size and that the peak position is well described by the phonon confinement model (PCM). For anatase nanocrystals with 15% brookite impurity, the spectrum shows an asymmetric band, which is formed mainly by the contributions of the anatase Eg and brookite A1g modes, with the brookite B1g and B3g peaks further broadening the band. In addition, the PCM no longer describes the peak position. These results show that even a small amount of brookite can have a strong influence on the Raman spectra of anatase/brookite-impurity samples.
Summary
Immune checkpoint therapy to reverse natural killer (NK) and T cell exhaustion has emerged as a promising treatment in various cancers. While anti‐programmed cell death 1 (PD‐1) pembrolizumab ...has recently gained Food and Drug Administration (FDA) approval for use in recurrent or metastatic cervical cancer, other checkpoint molecules, such as T cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine‐based inhibition motif (ITIM) domains (TIGIT) and T cell immunoglobulin and mucin‐domain containing‐3 (Tim‐3), have yet to be fully explored in this disease. We report expression of TIGIT, Tim‐3 and PD‐1 on subsets of peripheral blood NK (CD56dim/negCD16bright/dim/neg and CD56brightCD16dim/neg) and T cells. The percentages of these cells were increased in women with cervical cancer and pre‐malignant lesions. PD‐1+ NK and T cells were likely to co‐express TIGIT and/or Tim‐3. These cells, with an apparently ‘exhausted’ phenotype, were augmented in patients. A subset of cells were also natural killer group 2 member D (NKG2D)‐ and DNAX accessory molecule 1 (DNAM‐1)‐positive. PD‐1int and PD‐1high T cells were notably increased in cervical cancer. Soluble programmed cell death ligand 1 (PD‐L1) was higher in cancer patient blood versus healthy donors and we observed a positive correlation between sPD‐L1 and PD‐1+ T cells in women with low‐grade lesions. Within the cancer group, there were no significant correlations between sPD‐L1 levels and cervical cancer stage. However, when comparing cancer versus healthy donors, we observed an inverse association between sPD‐L1 and total T cells and a correlation between sPD‐L1 and CD56dim NK cells. Our results may show an overview of the immune response towards pre‐cancerous lesions and cervical cancer, perhaps giving an early clue as to whom to administer blocking therapies. The increase of multiple checkpoint markers may aid in identifying patients uniquely responsive to combined antibody therapies.
Overview of immune cells in the blood of patients with cervical cancer and precursor lesions. The co‐expression of checkpoint molecules PD‐1, TIGIT and Tim‐3 describe distinct NK and T cell populations that increase in accordance with disease progression. Tumor expression of checkpoint ligands, or soluble PD‐L1, may influence the development of these cells.
The planarian Schmidtea mediterranea is rapidly emerging as a model organism for the study of regeneration, tissue homeostasis and stem cell biology. The recent sequencing, assembly and annotation of ...its genome are expected to further buoy the biomedical importance of this organism. In order to make the extensive data associated with the genome sequence accessible to the biomedical and planarian communities, we have created the Schmidtea mediterranea Genome Database (SmedGD). SmedGD integrates in a single web-accessible portal all available data associated with the planarian genome, including predicted and annotated genes, ESTs, protein homologies, gene expression patterns and RNAi phenotypes. Moreover, SmedGD was designed using tools provided by the Generic Model Organism Database (GMOD) project, thus making its data structure compatible with other model organism databases. Because of the unique phylogenetic position of planarians, SmedGD (http://smedgd.neuro.utah.edu) will prove useful not only to the planarian research community, but also to those engaged in developmental and evolutionary biology, comparative genomics, stem cell research and regeneration.
•Cholinergic medial olivocochlear neurons are better preserved after long-term cortical electrical stimulation during aging, supporting a role of the efferent system in safeguarding aging progression ...in the cochlea.•Long-term cortical electrical stimulation during aging results in reduced age-related dystrophic degeneration of the stria vascularis and in inflammation markers, predicting functional recovery.•Long-term cortical electrical stimulation also results in increased calretinin immunolabeling in spiral ganglion neurons, suggesting primed upregulation for excitability modulation, potentially related with hearing loss compensation.•The observed changes induced by long-term cortical electrical simulation in the aging cochlea and brainstem, mirror reported auditory threshold recovery.
The auditory cortex is the source of descending connections providing contextual feedback for auditory signal processing at almost all levels of the lemniscal auditory pathway. Such feedback is essential for cognitive processing. It is likely that corticofugal pathways are degraded with aging, becoming important players in age-related hearing loss and, by extension, in cognitive decline. We are testing the hypothesis that surface, epidural stimulation of the auditory cortex during aging may regulate the activity of corticofugal pathways, resulting in modulation of central and peripheral traits of auditory aging. Increased auditory thresholds during ongoing age-related hearing loss in the rat are attenuated after two weeks of epidural stimulation with direct current applied to the surface of the auditory cortex for two weeks in alternate days (Fernández del Campo et al., 2024). Here we report that the same cortical electrical stimulation protocol induces structural and cytochemical changes in the aging cochlea and auditory brainstem, which may underlie recovery of age-degraded auditory sensitivity. Specifically, we found that in 18 month-old rats after two weeks of cortical electrical stimulation there is, relative to age-matched non-stimulated rats: a) a larger number of choline acetyltransferase immunoreactive neuronal cell body profiles in the ventral nucleus of the trapezoid body, originating the medial olivocochlear system.; b) a reduction of age-related dystrophic changes in the stria vascularis; c) diminished immunoreactivity for the pro-inflammatory cytokine TNFα in the stria vascularis and spiral ligament. d) diminished immunoreactivity for Iba1 and changes in the morphology of Iba1 immunoreactive cells in the lateral wall, suggesting reduced activation of macrophage/microglia; d) Increased immunoreactivity levels for calretinin in spiral ganglion neurons, suggesting excitability modulation by corticofugal stimulation. Altogether, these findings support that non-invasive neuromodulation of the auditory cortex during aging preserves the cochlear efferent system and ameliorates cochlear aging traits, including stria vascularis dystrophy, dysregulated inflammation and altered excitability in primary auditory neurons.
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