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Animals : An Open Access Journal From... May 2024Upon encountering a virus, fish initiate an innate immune response, guided by IFNs. Foxo3 plays a part in the body's immune response; however, its specific role in the...
Upon encountering a virus, fish initiate an innate immune response, guided by IFNs. Foxo3 plays a part in the body's immune response; however, its specific role in the IFN-guided immune response in fish is yet to be clarified. In this study, we characterized in Japanese medaka () and examined its role in the IFN-dependent immune response upon infection with the RGNNV. The results show that the coding region of the medaka gene is 2007 base pairs long, encoding 668 amino acids, and possesses a typical forkhead protein family structural domain. The product of this gene shares high homology with foxo3 in other fish species and is widely expressed, especially in the brain, eyes, testes, and heart. Upon RGNNV infection, mutant larvae showed a lower mortality rate, and adults exhibited a significant reduction in virus replication. Moreover, the absence of expression led to an increase in the expression of , and a decrease in the expression of other IFN-related genes such as and , implying that may function as a negative regulator in the antiviral signaling pathway. These findings provide crucial insights for disease-resistant breeding in the aquaculture industry.
PubMed: 38891634
DOI: 10.3390/ani14111587 -
Animals : An Open Access Journal From... May 2024Our prior research demonstrated a 20% to 25% reduction in bacterial chondronecrosis with osteomyelitis (BCO) lameness in broilers with organic Zn, Mn, and Cu (Availa...
Our prior research demonstrated a 20% to 25% reduction in bacterial chondronecrosis with osteomyelitis (BCO) lameness in broilers with organic Zn, Mn, and Cu (Availa ZMC) supplementation. Expanding on this, we investigated the optimal timing for Availa ZMC feeding to mitigate BCO lameness and reduce feed additive costs in the poultry industry. In this study, we compared the application of 0.15% Availa ZMC for 56 days, the first 28 days, and the last 28 days. The experimental design was a randomized block design involving 1560 one-day-old chicks distributed across two wire-floor pens as BCO source infection and four treatment groups with six replicates. The source of BCO infection exhibited a cumulative lameness incidence of 83%, whereas the negative control group showed a 77% cumulative incidence of lameness ( = 0.125). Administering 0.15% of Availa ZMC during the initial 28 d resulted in a 41.3% reduction in BCO incidence, significantly different from the supplementation during the last 28 d ( < 0.05). However, this reduction did not differ substantially ( > 0.05) from the 56d application period. Hence, administering 0.15% Availa ZMC during the first four weeks emerges as the optimal timing protocol, providing a defense against lameness comparable to the continuous supplementation throughout the complete production duration. Implementing this feeding approach reduces the cost of feed additive, promotes the health of skeletal bones, and effectively protects against BCO lameness in broilers, offering a valuable consideration for producers seeking optimal outcomes in the poultry industry.
PubMed: 38891572
DOI: 10.3390/ani14111526 -
BMC Plant Biology Jun 2024Wheat (Triticum aestivum L.) is one of the most important cereal crop species worldwide, but its growth and development are adversely influenced by drought stress....
Selenium and its nanoparticles modulate the metabolism of reactive oxygen species and morpho-physiology of wheat (Triticum aestivum L.) to combat oxidative stress under water deficit conditions.
BACKGROUND
Wheat (Triticum aestivum L.) is one of the most important cereal crop species worldwide, but its growth and development are adversely influenced by drought stress. However, the application of trace elements is known to improve plant physiology under water-limited conditions. In this study, the effects of drought stress on wheat plants were investigated, with a focus on potential mitigation by foliar application of selenium nanoparticles (Se(np)) and sodium selenate (NaSeO). The experiment was conducted in a net house using a completely randomized design with four replications. The treatments involved three levels of drought stress (mild, moderate, and severe) started at 30 days after sowing (DAS), with foliar sprays of Se(np) and Se (both 25 µM) initiated at 27 DAS and repeated 4 times at 7-day intervals until 55 DAS.
RESULTS
Drought stress significantly reduced plant growth, whereas Se(np) and Se sprays enhanced it. Drought stress induced chlorophyll degradation, increased malondialdehyde and hydrogen peroxide levels, impaired membrane stability, and caused electrolyte leakage. Severe drought stress reduced the levels of antioxidants (e.g., proline, ascorbate, and glutathione by 4.18-fold, 80%, and 45%) and the activities of antioxidant enzymes (ascorbate peroxidase, dehydroascorbate reductase, and others). Conversely, treatment with Se(np) and Se restored these parameters, for example, 1.23-fold higher total chlorophyll content with Se(np) treatment, 26% higher APX activity with Se treatment, 15% lower electrolyte leakage with Se treatment in wheat plants under severe drought stress. This Se-associated enhancement facilitated rapid scavenging of reactive oxygen species and reduced methylglyoxal toxicity, thereby diminishing oxidative stress and positively affecting the morphophysiological and biochemical responses of the plants under drought.
CONCLUSIONS
Drought-stressed wheat plants exhibited reductions in physiological processes, including water uptake and photosynthetic activity. However, Se(np) and Se applied at 25 µM mitigated the detrimental effects of drought. The application of Se(np) was notably more effective than the application of Se in mitigating drought stress, indicating the potential of the application of Se(np) as a sustainable agricultural practice under water-limited conditions.
Topics: Triticum; Oxidative Stress; Selenium; Reactive Oxygen Species; Nanoparticles; Droughts; Chlorophyll; Antioxidants; Dehydration; Hydrogen Peroxide
PubMed: 38890566
DOI: 10.1186/s12870-024-05282-3 -
Seizure May 2024Cognitive behavioural therapy (CBT) and other psychological approaches have a growing evidence base for treating Non-Epileptic Seizures (NES). However, communication... (Review)
Review
BACKGROUND
Cognitive behavioural therapy (CBT) and other psychological approaches have a growing evidence base for treating Non-Epileptic Seizures (NES). However, communication about the diagnosis can be difficult for clinicians and is not always well received. It is thought that Psychoeducation about NES may improve engagement with treatment such as CBT and may contribute to reductions in the frequency of seizures and improvements in health related quality of life. However, psychoeducational components of treatment are often not evaluated in isolation meaning the specific benefit to patients is not currently well understood.
AIMS
The researchers aimed to examine the outcomes associated with psychoeducational interventions and the content of these programmes for NES.
METHOD
A scoping review was undertaken across four databases with seventeen eligible studies identified which were charted to analyse the data.
RESULTS
Findings revealed that components and modalities of interventions varied as did methods of evaluating the interventions. A number of different outcome measures were used and not all studies reported the significance of findings. Results across studies were inconsistent; however, there was a general trend across the studies of symptom reduction and improvement in mental health.
CONCLUSIONS
Findings illustrate that psychoeducation has potential benefits as an intervention in its own right. However, it may be best placed as a second step in a stepped care model, between initial diagnosis and further psychological treatment. The present literature needs replication and more robust studies for more certain conclusions to be drawn.
PubMed: 38889520
DOI: 10.1016/j.seizure.2024.05.013 -
MedComm Jul 2024The association between Hepatitis B virus (HBV) infection and colorectal liver metastases (CRLM) remains ambiguous in current population-based evidence. To clarify this,...
The association between Hepatitis B virus (HBV) infection and colorectal liver metastases (CRLM) remains ambiguous in current population-based evidence. To clarify this, we present a retrospective analysis of 5871 colorectal cancer (CRC) patients. Propensity score matching (PSM) was applied to harmonize age and sex disparities within HBV+ ( = 1696) and HBV- ( = 4175) groups and further within HBV+ subgroups of chronic (CHB, = 474) and occult (OHB, = 1222) infections. Our initial results indicated a significant association between HBV infection and synchronous colorectal liver metastasis (SYN-CRLM); however, this association dissipated after PSM was employed to adjust for confounding variables. No significant association was observed between HBV infection and metachronous colorectal liver metastases (MET-CRLM) both before and after PSM. Further analysis revealed that HBV replication status did not influence the incidence of CRLM. However, HBV+ participants demonstrated an increased incidence of metachronous extrahepatic metastases, particularly to the lungs. Our findings imply that neither past nor present HBV infection is significantly correlated with the occurrence of SYN-CRLM or MET-CRLM. The absence of an association between HBV replication status and CRLM incidence highlights the importance of incorporating a broader range of factors in the clinical management of CRLM beyond the status of HBV infection.
PubMed: 38887467
DOI: 10.1002/mco2.584 -
Journal of the American College of... Jun 2024Patients hospitalized for COVID-19 frequently develop hypoxemia and acute respiratory distress syndrome (ARDS) after admission. In non-COVID-19 ARDS studies, admission...
OBJECTIVES
Patients hospitalized for COVID-19 frequently develop hypoxemia and acute respiratory distress syndrome (ARDS) after admission. In non-COVID-19 ARDS studies, admission to hospital wards with subsequent transfer to intensive care unit (ICU) is associated with worse outcomes. We hypothesized that initial admission to the ward may affect outcomes in patient with COVID-19 ARDS.
METHODS
This was a retrospective study of consecutive adults admitted for COVID-19 ARDS between March 2020 and March 2021 at Stanford Health Care. Mortality scores at hospital admission (Coronavirus Clinical Characterization Consortium Mortality Score [4C score]) and ICU admission (Simplified Acute Physiology Score III [SAPS-III]) were calculated, as well as ROX index for patients on high flow nasal oxygen. Patients were classified by emergency department (ED) disposition (ward-first vs. ICU-direct), and 28- and 60-day mortality and highest level of respiratory support within 1 day of ICU admission were compared. A second cohort (April 2021‒July 2022, = 129) was phenotyped to validate mortality outcome.
RESULTS
A total of 157 patients were included, 48% of whom were first admitted to the ward ( = 75). Ward-first patients had more comorbidities, including lung disease. Ward-first patients had lower 4C and similar SAPS-III score, yet increased mortality at 28 days (32% vs. 17%, hazard ratio [HR] 2.0, 95% confidence interval [95% CI] 1.0‒3.7, = 0.039) and 60 days (39% vs. 23%, HR 1.83, 95% CI 1.04‒3.22, = 0.037) compared to ICU-direct patients. More ward-first patients escalated to mechanical ventilation on day 1 of ICU admission (36% vs. 14%, = 0.002) despite similar ROX index. Ward-first patients who upgraded to ICU within 48 h of ED presentation had the highest mortality. Mortality findings were replicated in a sensitivity analysis.
CONCLUSION
Despite similar baseline risk scores, ward-first patients with COVID-19 ARDS had increased mortality and escalation to mechanical ventilation compared to ICU-direct patients. Ward-first patients requiring ICU upgrade within 48 h were at highest risk, highlighting a need for improved identification of this group at ED admission.
PubMed: 38887225
DOI: 10.1002/emp2.13192 -
Retrovirology Jun 2024An essential regulatory hub for retroviral replication events, the 5' untranslated region (UTR) encodes an ensemble of cis-acting replication elements that overlap in a... (Review)
Review
An essential regulatory hub for retroviral replication events, the 5' untranslated region (UTR) encodes an ensemble of cis-acting replication elements that overlap in a logical manner to carry out divergent RNA activities in cells and in virions. The primer binding site (PBS) and primer activation sequence initiate the reverse transcription process in virions, yet overlap with structural elements that regulate expression of the complex viral proteome. PBS-segment also encompasses the attachment site for Integrase to cut and paste the 3' long terminal repeat into the host chromosome to form the provirus and purine residues necessary to execute the precise stoichiometry of genome-length transcripts and spliced viral RNAs. Recent genetic mapping, cofactor affinity experiments, NMR and SAXS have elucidated that the HIV-1 PBS-segment folds into a three-way junction structure. The three-way junction structure is recognized by the host's nuclear RNA helicase A/DHX9 (RHA). RHA tethers host trimethyl guanosine synthase 1 to the Rev/Rev responsive element (RRE)-containing RNAs for m7-guanosine Cap hyper methylation that bolsters virion infectivity significantly. The HIV-1 trimethylated (TMG) Cap licenses specialized translation of virion proteins under conditions that repress translation of the regulatory proteins. Clearly host-adaption and RNA shapeshifting comprise the fundamental basis for PBS-segment orchestrating both reverse transcription of virion RNA and the nuclear modification of m7G-Cap for biphasic translation of the complex viral proteome. These recent observations, which have exposed even greater complexity of retroviral RNA biology than previously established, are the impetus for this article. Basic research to fully comprehend the marriage of PBS-segment structures and host RNA binding proteins that carry out retroviral early and late replication events is likely to expose an immutable virus-specific therapeutic target to attenuate retrovirus proliferation.
Topics: Virus Replication; RNA, Viral; Humans; HIV-1; 5' Untranslated Regions; Binding Sites; Gene Expression Regulation, Viral; Reverse Transcription; Retroviridae
PubMed: 38886829
DOI: 10.1186/s12977-024-00646-x -
The EMBO Journal Jun 2024Mutational patterns caused by APOBEC3 cytidine deaminase activity are evident throughout human cancer genomes. In particular, the APOBEC3A family member is a potent...
Mutational patterns caused by APOBEC3 cytidine deaminase activity are evident throughout human cancer genomes. In particular, the APOBEC3A family member is a potent genotoxin that causes substantial DNA damage in experimental systems and human tumors. However, the mechanisms that ensure genome stability in cells with active APOBEC3A are unknown. Through an unbiased genome-wide screen, we define the Structural Maintenance of Chromosomes 5/6 (SMC5/6) complex as essential for cell viability when APOBEC3A is active. We observe an absence of APOBEC3A mutagenesis in human tumors with SMC5/6 dysfunction, consistent with synthetic lethality. Cancer cells depleted of SMC5/6 incur substantial genome damage from APOBEC3A activity during DNA replication. Further, APOBEC3A activity results in replication tract lengthening which is dependent on PrimPol, consistent with re-initiation of DNA synthesis downstream of APOBEC3A-induced lesions. Loss of SMC5/6 abrogates elongated replication tracts and increases DNA breaks upon APOBEC3A activity. Our findings indicate that replication fork lengthening reflects a DNA damage response to APOBEC3A activity that promotes genome stability in an SMC5/6-dependent manner. Therefore, SMC5/6 presents a potential therapeutic vulnerability in tumors with active APOBEC3A.
PubMed: 38886582
DOI: 10.1038/s44318-024-00137-x -
BioRxiv : the Preprint Server For... Apr 2024Viral internal ribosomal entry sites (IRESs) form several classes that use distinct mechanisms to mediate end-independent initiation of translation. The origin of viral...
Viral internal ribosomal entry sites (IRESs) form several classes that use distinct mechanisms to mediate end-independent initiation of translation. The origin of viral IRESs is a longstanding question. The simplest IRESs comprise tandem pseudoknots and occur in the intergenic region (IGR) of genomes (order ). Larger IGR IRESs contain additional elements that determine specific properties such as binding to the head of the ribosoma l 40S subunit. Metagenomic analyses reported here identified novel groups of structurally distinct IGR-like IRESs. The smallest of these (∼120nt long) comprise three pseudoknots and bind directly to the ribosomal P site. Others are up to 260nt long: insertions occurred at specific loci, possibly reflecting non-templated nucleotide insertion during replication. Various groups can be arranged in order, differing by the cumulative addition of single structural elements, suggesting an accretion mechanism for the structural elaboration of IRESs. Identification of chimeric IRESs implicates recombinational exchange of domains as a second mechanism for the diversification of IRES structure. Recombination likely also accounts for the presence of IGR-like IRESs at the 5'-end of some dicistrovirus-like genomes (e.g. Hangzhou dicistrovirus 3) and in the RNA genomes of (order ), (order s), and the 'Ripiresk' picorna-like clade (order s).
PubMed: 38883778
DOI: 10.1101/2024.04.17.590008 -
ArXiv Jun 2024Electrical waves in the heart form rotating spiral or scroll waves during life-threatening arrhythmias such as atrial or ventricular fibrillation. The wave dynamics are...
Electrical waves in the heart form rotating spiral or scroll waves during life-threatening arrhythmias such as atrial or ventricular fibrillation. The wave dynamics are typically modeled using coupled partial differential equations, which describe reaction-diffusion dynamics in excitable media. More recently, data-driven generative modeling has emerged as an alternative to generate spatio-temporal patterns in physical and biological systems. Here, we explore denoising diffusion probabilistic models for the generative modeling of electrical wave patterns in cardiac tissue. We trained diffusion models with simulated electrical wave patterns to be able to generate such wave patterns in unconditional and conditional generation tasks. For instance, we explored the diffusion-based i) parameter-specific generation, ii) evolution and iii) inpainting of spiral wave dynamics, including reconstructing three-dimensional scroll wave dynamics from superficial two-dimensional measurements. Further, we generated arbitrarily shaped bi-ventricular geometries and simultaneously initiated scroll wave patterns inside these geometries using diffusion. We characterized and compared the diffusion-generated solutions to solutions obtained with corresponding biophysical models and found that diffusion models learn to replicate spiral and scroll waves dynamics so well that they could be used for data-driven modeling of excitation waves in cardiac tissue. For instance, an ensemble of diffusion-generated spiral wave dynamics exhibits similar self-termination statistics as the corresponding ensemble simulated with a biophysical model. However, we also found that diffusion models {produce artifacts if training data is lacking, e.g. during self-termination,} and `hallucinate' wave patterns when insufficiently constrained.
PubMed: 38883235
DOI: No ID Found