Aberrant autophagy is a major risk factor for inflammatory diseases and cancer. However, the genetic basis and underlying mechanisms are less established. UVRAG is a tumor suppressor candidate ...involved in autophagy, which is truncated in cancers by a frameshift (FS) mutation and expressed as a shortened UVRAG
. To investigate the role of UVRAG
in vivo, we generated mutant mice that inducibly express UVRAG
(iUVRAG
). These mice are normal in basal autophagy but deficient in starvation- and LPS-induced autophagy by disruption of the UVRAG-autophagy complex. iUVRAG
mice display increased inflammatory response in sepsis, intestinal colitis, and colitis-associated cancer development through NLRP3-inflammasome hyperactivation. Moreover, iUVRAG
mice show enhanced spontaneous tumorigenesis related to age-related autophagy suppression, resultant β-catenin stabilization, and centrosome amplification. Thus, UVRAG is a crucial autophagy regulator in vivo, and autophagy promotion may help prevent/treat inflammatory disease and cancer in susceptible individuals.
Decapods are an order of crustaceans which includes shrimps, crabs, lobsters and crayfish. They occur worldwide and are of great scientific interest as well as being of ecological and economic ...importance in fisheries and aquaculture. However, our knowledge of their biology mainly comes from the group which is most closely related to crustaceans - insects. Here we produce a de novo transcriptome database, crustacean annotated transcriptome (CAT) database, spanning multiple tissues and the life stages of seven crustaceans.
A total of 71 transcriptome assemblies from six decapod species and a stomatopod species, including the coral shrimp Stenopus hispidus, the cherry shrimp Neocaridina davidi, the redclaw crayfish Cherax quadricarinatus, the spiny lobster Panulirus ornatus, the red king crab Paralithodes camtschaticus, the coconut crab Birgus latro, and the zebra mantis shrimp Lysiosquillina maculata, were generated. Differential gene expression analyses within species were generated as a reference and included in a graphical user interface database at http://cat.sls.cuhk.edu.hk/. Users can carry out gene name searches and also access gene sequences based on a sequence query using the BLAST search function.
The data generated and deposited in this database offers a valuable resource for the further study of these crustaceans, as well as being of use in aquaculture development.
Different methods are used at Corteva
®
Agriscience to improve our understanding of mixing in large-scale mechanically agitated fermentors. These include (a) use of classical empirical correlations, ...(b) use of small-scale models, and (c) computational fluid dynamics (CFD). Each of these approaches has its own inherent strengths and limitations. Classic empirical or semi-empirical correlations can provide insights into mass transfer, blending, shear, and other important factors but are dependent on the geometry and condition used to develop the correlations. Laboratory-scale modelling can be very useful to study mixing and model the effect of heterogeneity on the culture, but success is highly dependent on the methodology applied. CFD provides an effective means to accelerate the exploration of alternative design strategies through physics-based computer simulations that may not be adequately described by existing knowledge or correlations. However, considerable time and effort is needed to build and validate these models. In this paper, we review the various approaches used at Corteva Agriscience to deepen our understanding of mixing in large-scale fermentation processes.
Background Oral mucositis (OM) in patients receiving cancer therapy is thus far not well managed with standard approaches. We aimed to assess the safety and effectiveness of methylene blue (MB) oral ...rinse for OM pain in patients receiving cancer therapy. Methods In this randomized, single-blind phase 2 clinical trial, patients were randomized to one of four arms: MB 0.025%+conventional therapy (CTx) (n = 15), MB 0.05%+CTx (n = 14), MB 0.1%+CTx (n = 15), or CTx alone (n = 16). Intervention groups received MB oral rinse every 6 h for 2 days with outcomes measured at days 1-2; safety was evaluated up to 30 days. The primary outcome measured change in the pain numeric rating scale (0-10) from baseline to day 2. Secondary outcome measured change in oral function burden scores from baseline to day 2, World Health Organization OM grades, morphine equivalent daily doses, and adverse events. The trial was registered with ClinicalTrials.gov ID: NCT03469284. Results Sixty patients (mean age 43, range 22-62 years) completed the study. Compared with those who received CTx alone, those who received MB had a significant reduction of pain scores at day 2 of treatment (mean + or - SD); 0.025%: 5.2 + or - 2.9, 0.05%: 4.5 + or - 2.9, 0.1%: 5.15 + or - 2.6) and reduction of oral function burden scores (0.025%: 2.5 + or - 1.55, 0.05%: 2.8 + or - 1.7, 0.1%: 2.9 + or - 1.60). No serious adverse events were noted, but eight patients reported burning sensation of the oral cavity with the first dose, and this caused one patient to discontinue therapy. Conclusions MB oral rinse showed significant pain reduction and improved oral functioning with minimal adverse effects. Trial registration ClinicalTrials.gov ID: NCT03469284. Keywords: Oral mucositis, Cancer therapy, Methylene blue Oral Rinse
Positional behaviors have been broadly quantified across the Order Primates, and in several other mammalian lineages, to contextualize adaptations to, and evolution within, an arboreal environment. ...Outside of Mammalia, however, such data are yet to be reported. In this study, we present the first quantitative report of positional behavior within Aves, presenting 11,246 observations of scan sampling data from a colony of Monk Parakeets (Myiopsitta monachus) from Brooklyn, New York City. Each scan recorded locomotor and postural behavior and information about weather condition, temperature, and substrate properties (e.g., type, size, orientation). A distinction was also recorded between natural and artificial substrates. Parrots exhibited a strong preference for small and terminal branches, a selection which may reflect targeted foraging of new fruit growth and leaf-buds. We further observed that the gait transition from walking to sidling appears primarily driven by substrate size, with the former preferred on the ground and on large, broad substrates and the latter used to navigate smaller branches. Finally, we observed an increase in locomotor diversity on artificial versus naturally occurring substrates. This demonstrates the importance of a flexible behavioral repertoire in facilitating a successful transition towards an urban landscape in introduced species.
Oral mucositis is a common and often debilitating complication among cancer patients receiving radiation therapy to the head and neck or chemotherapy agents, or undergoing hematopoietic stem cell ...transplantation. Pain and decreased oral function associated with oral mucositis may persist long after the conclusion of therapy. Although most patients respond to conservative management, a subset of patients develops intractable pain with severe consequences. For some, the use of total parenteral nutrition with insertion of percutaneous endoscopic gastrostomy feeding tubes is the only alternative. Current recommendations to treat mucositis and its related pain include basic oral care, bland oral rinses, topical anesthetics, and systemic analgesics. We believe that chemical neurolysis of the affected areas with methylene blue used as an oral rinse is a noninvasive, efficient, safe, and cost‐effective alternative that can provide prolonged analgesia in patients with intractable pain of oral mucositis. The benefits of this therapy are reflected in its improvement of patients’ quality of life by enabling oral feeding and controlling pain. We report a series of 5 consecutive patients with intractable oral mucositis‐related pain despite conventional treatment with systemic opiates. All 5 patients responded well to the use of 0.05% methylene blue as mouth rinse, demonstrating sustained analgesia over 3 weeks. The treatment was tolerated well, and overall patient satisfaction was very high. We also observed that methylene blue rinse significantly reduced the total opioid requirement, as demonstrated by reductions in the patients’ morphine equivalent daily dose scores after its use. Our case series suggests that 0.5% methylene blue oral rinse therapy is an effective and inexpensive modality that can be used safely to palliate intractable oral pain in patients with mucositis associated with cancer treatment. To our knowledge, this is the first report using this therapy to treat pain from oral mucositis.
Metacognitive abilities, the capacity to think about one’s own thinking processes, offer a range of advantages that may drive their evolution in non-primate animals (NPAs). These advantages include ...enhancing adaptive decision-making in uncertain situations, efficient resource management, error detection and correction, and facilitating complex social interactions and problem-solving. In this comprehensive study, we have chosen two key paradigms — namely, uncertainty monitoring and information-seeking tasks — to study metacognitive phenomena in NPAs. The first paradigm involves an extensive meta-analysis of existing research, shedding light on how NPAs monitor and respond to uncertainty. We then transition to the second paradigm, which focuses on information-seeking behaviors, employing a different analytical approach. Our study aims to provide a holistic understanding of these cognitive processes in NPAs, contributing valuable insights into their cognitive complexity and ecological contexts. Through a coverage of 30 articles spanning 13 different NPA species, we bridge gaps in our understanding of metacognition beyond primates and explore potential divergent evolutionary paths, challenging assumptions about cognitive capability in NPAs.
Drug-sensitive live coccidiosis vaccines have been used to control coccidiosis and renew drug sensitivity in commercial chicken operations. However, only limited species coverage vaccines have been ...available for commercial turkey producers. This study aimed to assess the effect of an
vaccine candidate, with and without amprolium intervention, on performance and oocyst shedding. Additionally, the effect of vaccination, amprolium treatment, and
challenge on intestinal integrity and microbiome composition was evaluated.
Experimental groups included: (1) NC (non-vaccinated, non-challenged control); (2) PC (non-vaccinated, challenged control); (3) VX + Amprol (
candidate vaccine + amprolium); and 4) VX (
candidate vaccine). For VX groups, 50% of the direct poults were orally vaccinated at DOH with 50 sporulated
oocysts and were comingled with contact or non-vaccinated poults for the duration of the study. From d10-14, VX + Amprol group received amprolium (0.024%) in the drinking water. All groups except NC were orally challenged with 95K
sporulated oocysts/mL/poult at d23. At d29, ileal and cecal contents were collected for 16S rRNA gene-based microbiome analysis.
VX did not affect performance during the pre-challenge period. At d23-29 (post-challenge), VX groups had significantly (
< 0.05) higher BWG than the PC group. Contacts and directs of VX groups in LS had significantly reduced compared to PC. As anticipated, amprolium treatment markedly reduced fecal and litter OPG for the VX + Amprol group compared to the VX group which did not receive amprolium. The ileal and cecal content results showed that the PC group had different bacterial diversity and structure, including alpha and beta diversity, compared to NC. Linear discriminant analysis Effect Size (LEfSe) identified that
(ASV2) was enriched in PC's ileal and cecal content. Compared to NC and PC, the vaccinated groups showed no distinct clusters, but there were similarities in the ileal and cecal communities based on Bray-Curtis and Jaccard distances. In conclusion, these results indicate that vaccination with this strain of
, with or without amprolium intervention, caused a very mild infection that induced protective immunity and challenge markedly affected both the ileal and cecal microbiome.
A mixed
Eimeria
spp. challenge model was designed to assess the effects of challenge on broiler chicken performance, intestinal integrity, and the gut microbiome for future use to evaluate ...alternative strategies for controlling coccidiosis in broiler chickens. The experimental design involved broiler chickens divided into two groups: a control group (uninfected) and a positive control group, infected with
Eimeria acervulina
(EA),
Eimeria maxima
(EM), and
Eimeria tenella
(ET). At day-of-hatch, 240 off-sex male broiler chicks were randomized and allocated to one of two treatment groups. The treatment groups included: (1) Non-challenged (NC,
n
= 5 replicate pens); and (2) challenged control (PC,
n
= 7 replicate pens) with 20 chickens/pen. Pen weights were recorded at d0, d16, d31, d42, and d52 to determine average body weight (BW) and (BWG). Feed intake was measured at d16, d31, d42, and d52 to calculate feed conversion ratio (FCR). Four diet phases included a starter d0–16, grower d16–31, finisher d31–42, and withdrawal d42–52 diet. At d18, chickens were orally challenged with 200 EA, 3,000 EM, and 500 ET sporulated oocysts/chicken. At d24 (6-day post-challenge) and d37 (19-day post-challenge), intestinal lesion scores were recorded. Additionally, at d24, FITC-d was used as a biomarker to evaluate intestinal permeability and ileal tissue sections were collected for histopathology and gene expression of tight junction proteins. Ileal and cecal contents were also collected to assess the impact of challenge on the microbiome. BWG and FCR from d16–31 was significantly (
p
< 0.05) reduced in PC compared to NC. At d24, intestinal lesion scores were markedly higher in the PC compared to the NC. Intestinal permeability was significantly increased in the PC group based on serum FITC-d levels. Cadherin 1 (CDH1), calprotectin (CALPR), and connexin 45 (Cx45) expression was also upregulated in the ileum of the PC group at d24 (6-day post-challenge) while villin 1 (VIL1) was downregulated in the ileum of the PC group. Additionally,
Clostridium perfringens
(ASV1) was enriched in the cecal content of the PC group. This model could be used to assess the effect of alternative coccidiosis control methods during the post-challenge with EA, EM, and ET.
Abstract
Objective
The objective of this study was to characterize the utility of calcitonin gene–related peptide (CGRP) and nerve growth factor (NGF) as potential biomarkers for headache and pain ...disorders in the post–military deployment setting.
Background
The need to improve recognition, assessment, and prognoses of individuals with posttraumatic headache or other pain has increased interest in the potential of CGRP and NGF as biomarkers.
Methods
The Warrior Strong Study (NCT01847040) is an observational longitudinal study of United States–based soldiers who had recently returned from deployment to Afghanistan or Iraq from 2009 to 2014. The present nested cross‐sectional analysis uses baseline data collected from soldiers returning to Fort Bragg, North Carolina.
Results
In total, 264 soldiers (mean (standard deviation SD age 28.1 6.4 years, 230/264 87.1% men, 171/263 65.0% White) were analyzed. Mean (SD) plasma levels of CGRP were 1.3 (1.1) pg/mL and mean levels of NGF were 1.4 (0.4) pg/mL. Age was negatively correlated with NGF (−0.01 pg/mL per year,
p
= 0.007) but was not associated with CGRP. Men had higher mean (SD) CGRP plasma levels than women (1.4 95% confidence interval CI; 1.2 vs. 0.9 95% CI 0.5 pg/mL,
p
< 0.002, Kruskal–Wallis test). CGRP levels were lower in participants who had a headache at the time of the blood draw (1.0 0.6 pg/mL vs. 1.4 1.2 pg/mL,
p
= 0.024). NGF was lower in participants with continuous pain (all types; 1.2 0.4 vs. 1.4 0.4 pg/mL,
p
= 0.027) and was lower in participants with traumatic brain injury (TBI) + posttraumatic headache (PTH) versus TBI without PTH (1.3 0.3 vs. 1.4 0.4 pg/mL,
p
= 0.021). Otherwise, CGRP and NGF were not associated with migraine‐like headache, TBI status, or headache burden as measured by the number of medical encounters in crude or adjusted models.
Conclusion
In this exploratory study, plasma levels of NGF and CGRP showed promise as biomarkers for headache and other types of pain. These findings need to be replicated in other cohorts.
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