The Role of Microglia and Macrophages in Modulating Brain Neural Activity in Larval Zebrafish

In vertebrates, macrophages are critical innate immune cells of which a specialized subset called microglia resides in the brain integrated with neurons and other glial cells. While microglia have been implicated for many functions in the brain, it has remained unclear whether these immune cells can influence animal behaviors though modulating brain neural circuits. We hypothesized that microglia are intricately interconnected with neuronal activity and thus neural circuit function, thereby able to alter behavioral outputs of brain functions. We sought to use genetic models, namely the microglia-lacking zebrafish nlrc3l and irf8 mutants, to understand whether eliminating the normal interactions of microglia in the brain could lead to altered behaviors. We performed large-scale, long-term movement tracking and found a highly significant reduction in spontaneous locomotion during daytime in the nlrc3l mutants, while the other microglia-lacking mutant (irf8 mutant) exhibited only a modest difference. We also analyzed the pattern of movement over the long-term tracking, and found no significant difference between the mutants from control animals, indicating the phenotype was specific to a decrease in spontaneous activity rather than a defect in pattern of movement or ability to move. Using in vivo whole-brain calcium imaging, we found a strong reduction in baseline neural firing in the diencephalic neurons of the nlrc3l mutants. Further analysis of additional brain regions and other microglia-lacking mutants will better define specific neural circuits susceptible to microglial regulation, thereby altered in the absence of microglia. This study provides evidence supporting the role of microglia in modulating neural circuits that regulate normal spontaneous behaviors at steady state and the possibility that the presence of inflammation can exacerbate the behavioral deficiency when microglia are impaired. Insights from our zebrafish paradigm can shed light on neuroimmune interactions that likely will be relevant to these processes in human as many genetic pathways and cellular mechanisms are conserved between zebrafish and human.Bachelor of Scienc

Pengaruh Pemberian Terapi Minyak Nigella Sativa Dan Kombinasinya Dengan Seftriakson Terhadap Jumlah Kuman Methicillin Resistant Staphylococcus Aureus (Mrsa) Pada Kultur Limpa Mencit Balb/c

Background: Levels of serum albumin can be used as a predictor of morbidity and mortality in the elderly. Reduced serum albumin concentration can be caused by oxidative modification due to aging or insufficient protein intake. SOD as an enzymatic antioxidant might prevent oxidative stress so that albumin modification process can be inhibited. SOD supplementation was expected to increase serum albumin levels.Aim: To prove the effect of Nigella sativa oil and its combination with ceftriaxone toward MRSA count in BALB/c mice\u27s spleen culture.Methods: This was true laboratory experimental study with post test only control group design. The samples were 20 males BALB/c mice, randomized into 4 groups. Control was given 0,03 ml aquabidest injected intraperitoneally, P1 was given 0,03 ml ceftriaxone injected intraperitoneally, P2 was given 0,3 ml Nigella sativa oil orally and P3 was given the combination of 0,03 ml ceftriaxone and 0,3 ml Nigella sativa oil. 0,2 ml (107 cfu/ml) MRSA was injected intraperitoneally at the hour 0. The treatment was given at the hour 16 and mice were terminated at the hour 24. Kruskall-Wallis Test and Mann-Whitney Test is used to analyze the data.Results: Results of the mean number of MRSA bacteria in spleen culture were K=124x103 160,70x103; P1=24,08x103 26,53x103; P2=0,78x103 1,52x103; P3=6,05x103 13,38x103. The number of MRSA bacteria decreased significantly between control group compared to P2 (p=0,016) and P3 (p=0,046) and P1 compared to P2 (p=0,016) and P3 (p=0,047). There were no significance between control compared to P1 (p=0,674) and P2 toward P3 (p=0,596).Conclusion: Administration of Nigella sativa oil and its combination with ceftriaxone can decrease the number of MRSA bacteria in BALB/c mice\u27s spleen cultures

Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention

Quantitative proteomic analysis reveals the involvement of mitochondrial proteins in tomato fruit ripening

Fruit ripening is characterized by dramatic changes in fruit quality and is considered to influence postharvest storage. The mitochondria are one of the most important organelles that play crucial roles in fruit quality formation, but the underlying mechanisms remain unclear. In this study, the expression profiles of mitochondrial proteins during tomato fruit ripening were investigated using quantitative proteomic analysis, leading to the identification of 27 proteins which showed altered abundance. We additionally evaluated changes in the mitochondrial proteome in the ripening-deficient mutant, ripening-inhibitor (rin), which carries a mutation in the transcription factor RIN. A total of 74 proteins were identified which changed abundance significantly in the rin mutant. Gene expression analysis combined with chromatin immunoprecipitation indicated that four genes, DnaK, HSP, PYP, and ACC, which encode chaperone DnaK, heat shock protein, pyruvate kinase, and acetyl-CoA carboxylase, respectively, are direct targets of RIN. These results suggest that mitochondria might participate in the regulation of fruit quality and ripening by specific proteins. Our findings provide new information to unravel of gene regulatory networks that control fruit quality and ripening

A Neural-Inspired Architecture for EEG-Based Auditory Attention Detection

10.1109/THMS.2022.317621

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Comparison of the LLP models in Singapore, the U.K. and the U.S

Post-transcriptional regulation of fruit ripening and disease resistance in tomato by the vacuolar protease SlVPE3

Background: Proteases represent one of the most abundant classes of enzymes in eukaryotes and are known to play key roles in many biological processes in plants. However, little is known about their functions in fruit ripening and disease resistance, which are unique to flowering plants and required for seed maturation and dispersal. Elucidating the genetic mechanisms of fruit ripening and disease resistance is an important goal given the biological and dietary significance of fruit. Results: Through expression profile analyses of genes encoding tomato (Solanum lycopersicum) cysteine proteases, we identify a number of genes whose expression increases during fruit ripening. RNA interference (RNAi)-mediated repression of SlVPE3, a vacuolar protease gene, results in alterations in fruit pigmentation, lycopene biosynthesis, and ethylene production, suggesting that SlVPE3 is necessary for normal fruit ripening. Surprisingly, the SlVPE3 RNAi fruit are more susceptible to the necrotrophic pathogen Botrytis cinerea. Quantitative proteomic analysis identified 314 proteins that differentially accumulate upon SlVPE3 silencing, including proteins associated with fruit ripening and disease resistance. To identify the direct SlVPE3 targets and mechanisms contributing to fungal pathogen resistance, we perform a screening of SlVPE3-interacting proteins using co-immunoprecipitation coupled with mass spectrometry. We show that SlVPE3 is required for the cleavage of the serine protease inhibitor KTI4, which contributes to resistance against the fungal pathogen B. cinerea. Conclusions: Our findings contribute to elucidating gene regulatory networks and mechanisms that control fruit ripening and disease resistance responses

The prevalence and under-diagnosis of vertebral fractures on chest radiograph

Abstract Background Vertebral fracture is the most common fragility fracture but it remains frequently unrecognized and is underdiagnosed worldwide. In this retrospective study, we examined the prevalence of moderate and severe vertebral fractures on chest radiographs of hospitalized female patients aged 50 years and older and determined missed diagnosis of vertebral fractures in the original radiology reports. Methods 3216 female patients 50 years of age and older were enrolled in our study. The patients’ medical records including their original radiology reports and lateral chest radiographs were retrospectively reviewed by the study radiologists who had training certificates from the International Society for Clinical Densitometry (ISCD). Vertebral fractures between thoracic spine T4 and lumbar spine L1 were identified and classified using Genant’s semi-quantitative scale. The definition of vertebral fractures used in this study was Genant grade 2 or higher. Results The study radiologists identified 295(9.2%) patients with grade 2 or 3 fractured vertebrae, total 444 vertebrae on 3216 chest radiographs. The prevalence of vertebral fracture was 2.4% in women aged 50-59 yrs., 8.9% in women aged 60–69 yrs., and 21.9% in women aged≥70 yrs. There were 213 patients with a single vertebral fracture, 49 patients with two vertebral fractures and 33 patients with ≥ three vertebral fractures. Fractured vertebrae were identified with greater frequency in thoracic spine T11,12 and lumbar spine L1. According to our statistics, 66.8% of patients with vertebral fractures found in this study were undiagnosed in the original radiology reports. Conclusions Vertebral fracture is common on chest radiographs but it is often ignored by radiologists. Genant’s semiquantitative assessment is a simple and effective method for detecting vertebral fracture. Because osteoporotic vertebral fracture increases the risk of new fractures, radiologists have an important role in accurately diagnosing vertebral fractures