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Lastly, we discuss recently published evidence from a progressive model of PD suggesting that contrary to the classical model, striatal pathway imbalance is necessary but not sufficient to produce frank parkinsonism.It is known that the exact neurons maintaining a given memory (the neural ensemble) change from trial to trial. This raises the question of how the brain achieves stability in the face of this representational drift. Here, we demonstrate that this stability emerges at the level of the electric fields that arise from neural activity. We show that electric fields carry information about working memory content. The electric fields, in turn, can act as "guard rails" that funnel higher dimensional variable neural activity along stable lower dimensional routes. We obtained the latent space associated with each memory. We then confirmed the stability of the electric field by mapping the latent space to different cortical patches (that comprise a neural ensemble) and reconstructing information flow between patches. Stable electric fields can allow latent states to be transferred between brain areas, in accord with modern engram theory.Recent advances in diffusion-weighted imaging have enabled us to probe the microstructure of even gray matter non-invasively. However, these advanced multi-shell protocols are often not included in large-scale studies as they significantly increase scan time. In this study, we investigated whether one set of multi-shell diffusion metrics commonly used in gray matter (as derived from Neurite Orientation Dispersion and Density Imaging, NODDI) provide enough additional information over typical tensor and volume metrics to justify the increased acquisition time, using the cognitive aging framework in the human hippocampus as a testbed. We first demonstrated that NODDI metrics are robust and reliable by replicating previous findings from our lab in a larger population of 79 younger (20.41 ± 1.89 years, 46 females) and 75 older (73.56 ± 6.26 years, 45 females) adults, showing that these metrics in the hippocampal subfields are sensitive to age and memory performance. We then asked how these subfield specific hippocampal NODDI metrics compared with standard tensor metrics and volume in predicting age and memory ability. We discovered that both NODDI and tensor measures separately predicted age and cognition in comparable capacities. However, integrating these modalities together considerably increased the predictive power of our logistic models, indicating that NODDI and tensor measures may be capturing independent microstructural information. We use these findings to encourage neuroimaging data collection consortiums to include a multi-shell diffusion sequence in their protocols since existing NODDI measures (and potential future multi-shell measures) may be able to capture microstructural variance that is missed by traditional approaches, even in studies exclusively examining gray matter.Biofilms contribute to the resistance of Edwardsiella tarda to antibiotics and host immunity. tetrathiomolybdate AroC in the shikimate pathway produces chorismate to synthesize crucial intermediates such as indole. In this study, the differences between biofilms produced by aroC mutants (△aroC), wild-type (WT) strains, and △aroC complementary strains (C△aroC) were detected both in vitro with 96-well plates, tubes, or coverslips and in vivo using a mouse model of subcutaneous implants. When examining potential mechanisms, we found that the diameters of the movement rings in soft agar plates and the flagellar sizes and numbers determined by silver staining were all lower for △aroC than for WT and C△aroC. Moreover, qRT-PCR showed that the transcription levels of flagellar synthesis genes, fliA and fliC, were reduced in △aroC. AroC, FliC, or FliA may accompany the motility of △aroC strains. In addition, compared with the WT and C△aroC, the amounts of indole in △aroC were significantly decreased. Notably, the formation of biofilms by these strains could be promoted by exogenous indole. Therefore, the aroC gene could affect the biofilm formation of E. tarda concerning its impact on flagella and indole.The effects of vitamin D supplementation on cardiovascular diseases are controversial. Data on effects of vitamin D upon cardiac biomarkers, as surrogate endpoints of cardiovascular diseases, are limited and inconclusive. Therefore, we carried out a post-hoc analysis of sub-samples of a randomized, double-blinded, placebo-controlled trial with community-based older adults who were randomized to receive monthly 100,000-IU vitamin D or placebo, to determine effect of monthly vitamin D supplementation on high-sensitivity cardiac troponin I (hs-cTnI), troponin T (hs-cTnT) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP). Adjusted relative difference (aRD) of follow-up geometric mean of biomarkers and adjusted relative risk (aRR) of elevated biomarkers between two groups were calculated. A total of 779 participants aged 50-84 y, randomized to vitamin D (n = 395) or placebo (n = 384) groups underwent sampling for measurement of plasma biomarkers at baseline and after one or two years treatment. Over a meanin D status, vitamin D treatment was associated, on follow up and change from baseline, with lower plasma NT-proBNP compared with placebo. This potentially signals reduced risk of subsequent heart failure within this sub-group. However, we acknowledge that these findings need to be considered exploratory. Further research is required to replicate them.In this paper we tested how oxysterols influence on fusion process between viral lipid envelope and host cells membranes. For this purpose, the Zika virus was selected, while dendritic cell (DC) and neural cell (NC) membranes were chosen as target membranes. The investigated systems were modeled as multicomponent Langmuir monolayers and characterized using surface manometry and imaging in micro- (Brewster angle microscopy, BAM) and nanoscale (Atomic Force Microscopy, AFM) to monitor local heterogeneity. The fusion process was conducted by mixing viral and host cell membranes devoid and in the presence of oxysterols 25-hydroxycholesterol (25-OH) and 7β-hydroxycholesterol (7β-OH) as representatives of chain- and ring-oxidized oxysterols, respectively. Our results show that oxysterols hinder the fusion with host cell membranes by modifying their biophysical properties. Moreover, oxysterols applied to an already infected membrane reverse the changes caused by the infection. It could therefore be concluded that oxysterols may display antiviral activity in two ways they prevent the healthy membrane from viral infection by blocking the fusion process; and protect already infected membrane from pathological changes induced by the virus.Ovarian cancer is a fatal malignancy in women with a low survival rate that demands new therapeutic paradigms. Cancer cells acquire various exclusive alterations to proliferate, invade, metastasize, and escape cell death, acting independently of growth-inducing or growth-inhibiting signals. The nature of cellular signaling in tumorigenesis is interwoven. Wnt signaling is an evolutionarily conserved signaling cascade that has been shown to regulate ovarian cancer pathogenesis. The molecular mechanism of Wnt signaling underlying the development of ovarian cancer, drug resistance, and relapse is not completely understood. Extracellularly secreted Wnt signaling inhibitors are crucial regulators of ovarian cancer tumorigenesis and malignant properties of cancer stem cells. Wnt inhibitors arbitrated modifications affecting Wnt pathway proteins on the cell membranes, in the cytoplasm, and in the nucleus have been shown to span essential contributions in the initiation, progression, and chemoresistance of ovarian cancer. Although many extrinsic inhibitors developed targeting the downstream components of the Wnt signaling pathway, investigating the molecular mechanisms of endogenous secreted inhibitors might substantiate prognostic or therapeutic biomarkers development. Given the importance of Wnt signaling in ovarian cancer, more systematic studies combined with clinical studies are requisite to probe the precise mechanistic interactions of Wnt antagonists in ovarian cancer. This review outlines the latest progress on the Wnt antagonists and ovarian cancer-specific regulators such as micro-RNAs, small molecules, and drugs regulating these Wnt antagonists in ovarian tumourigenesis.
In hospital hygiene, it remains unclear to what extent surface contamination might represent a potential reservoir for nosocomial pathogens. This study investigates the effects of different sanitization strategies on the microbial structures and the ecological balance of the environmental microbiome in the clinical setting.
Three cleaning regimes (disinfectants, detergents, and probiotics) were applied subsequently in nine independent patient rooms at a neurological ward (Charité, Berlin). Weekly sampling procedures included three different environmental sites floor, door handle, and sink. Characterization of the environmental microbiota and detection of antibiotic resistance genes (ARGs) were performed by 16S rRNA sequencing and multiplex Taq-Man qPCR assays, respectively.
Our results showed a displacement of the intrinsic environmental microbiota after probiotic sanitization, which reached statistical significance in the sink samples (median 16S-rRNA copies=138.3; IQR 24.38-379.5) when compared to traditional disinfection measures (median 16S rRNA copies=1343; IQR 330.9-9479; p<0.05). This effect was concomitant with a significant increase in the alpha-diversity metrics in both the floor (p<0.001) and the sink samples (p<0.01) during the probiotic strategy. We did not observe a sanitization-dependent change in relative pathogen abundance at any tested site, but there was a significant reduction in the total ARG counts in the sink samples during probiotic cleaning (mean ARGs/sample 0.095±0.067) when compared to the disinfection strategy (mean ARGs/sample 0.386±0.116; p<0.01).
The data presented in this study suggest that probiotic sanitization is an interesting strategy in hospital hygiene management to be further analyzed and validated in randomized clinical studies.
The data presented in this study suggest that probiotic sanitization is an interesting strategy in hospital hygiene management to be further analyzed and validated in randomized clinical studies.Camellia vietnamensis Huang, which belongs to Camellia oleifera, is a traditional Chinese medicinal plant widely planted on Hainan Island. Tea saponin is an important functional component of C. vietnamensis, and squalene is the precursor substance that controls its formation. Squalene synthase (SQS EC 2.5.1.21) synthesizes squalene from 2 molecules of farnesyl pyrophosphate (FPP). In this study, 1683 bp of the C. vietnamensis SQS gene, designated as CvSQS, was cloned and encoded 414 amino acids. Bioinformatics and phylogenetic tree analysis revealed the high homology of CvSQS with squalene synthases from other plants. For soluble proteins, the carboxy-terminal deleted CvSQS was obtained for expression in Escherichia coli Transetta (DE3), and the recombinant protein with a weight of 42.5 kDa was detected using SDS-PAGE and Western blot. After an enzymatic reaction, the presence of squalene in the product was analyzed using GC-MS detection, which indicated that CvSQS had catalytic activity. The tissue specificity of CvSQS and its presence in seeds at various ripening stages was detected by q-RT PCR.