Biglycan promotes hepatic fibrosis through activating heat shock protein 47.

BACKGROUND: Biglycan (BGN) is a small leucine-rich proteoglycan that participates in the production of excess extracellular matrix (ECM) and is related to fibrosis in many organs. However, the role of BGN in liver fibrosis remains poorly understood. This study aimed to investigate the role and mechanism of BGN in liver fibrosis. METHODS: Human liver samples, Bgn-/0 (BGN KO) mice and a human LX-2 hepatic stellate cells (HSCs) model were applied for the study of experimental fibrosis. GEO data and single-cell RNA-seq data of human liver tissue were analysed as a bioinformatic approach. Coimmunoprecipitation, immunofluorescence staining, western blotting and qRT-PCR were conducted to identify the regulatory effects of BGN on heat shock protein 47 (HSP47) expression and liver fibrosis. RESULTS: We observed that hepatic BGN expression was significantly increased in patients with fibrosis and in a mouse model of liver fibrosis. Genetic deletion of BGN disrupted TGF-ß1 pathway signalling and alleviated liver fibrosis in mice administered carbon tetrachloride (CCl4 ). siRNA-mediated knockdown of BGN significantly reduced TGF-ß1-induced ECM deposition and fibroblastic activation in LX-2 cells. Mechanistically, BGN directly interacted with and positively regulated the collagen synthesis chaperon protein HSP47. Rescue experiments showed that BGN promoted hepatic fibrosis by regulating ECM deposition and HSC activation by positively regulating HSP47. CONCLUSION: Our data indicate that BGN promotes hepatic fibrosis by regulating ECM deposition and HSC activation through an HSP47-dependent mechanism. BGN may be a new biomarker of hepatic fibrosis and a novel target for disease prevention and treatment.

Mineralization of Few-Layer Graphene Made It Bioavailable in Chlamydomonas reinhardtii.

Numerous studies have emphasized the toxicity of graphene-based nanomaterials to algae, however, the fundamental behavior and processes of graphene in biological hosts, including its transportation, metabolization, and bioavailability, are still not well understood. As photosynthetic organisms, algae are key contributors to carbon fixation and may play an important role in the fate of graphene. This study investigated the biological fate of 14C-labeled few-layer graphene (14C-FLG) in Chlamydomonas reinhardtii (C. reinhardtii). The results showed that 14C-FLG was taken up by C. reinhardtii and then translocated into its chloroplast. Metabolomic analysis revealed that 14C-FLG altered the metabolic profiles (including sugar metabolism, fatty acid, and tricarboxylic acid cycle) of C. reinhardtii, which promoted the photosynthesis of C. reinhardtii and then enhanced their growth. More importantly, the internalized 14C-FLG was metabolized into 14CO2, which was then used to participate in the metabolic processes required for life. Approximately 61.63%, 25.31%, and 13.06% of the total radioactivity (from 14CO2) was detected in carbohydrates, lipids, and proteins of algae, respectively. Overall, these results reveal the role of algae in the fate of graphene and highlight the potential of available graphene in bringing biological effects to algae, which helps to better assess the environmental risks of graphene.

Laminar-specific functional connectivity mapping with multi-slice line-scanning fMRI.

Despite extensive studies detecting laminar functional magnetic resonance imaging (fMRI) signals to illustrate the canonical microcircuit, the spatiotemporal characteristics of laminar-specific information flow across cortical regions remain to be fully investigated in both evoked and resting conditions at different brain states. Here, we developed a multislice line-scanning fMRI (MS-LS) method to detect laminar fMRI signals in adjacent cortical regions with high spatial (50 µm) and temporal resolution (100 ms) in anesthetized rats. Across different trials, we detected either laminar-specific positive or negative blood-oxygen-level-dependent (BOLD) responses in the surrounding cortical region adjacent to the most activated cortex under the evoked condition. Specifically, in contrast to typical Layer (L) 4 correlation across different regions due to the thalamocortical projections for trials with positive BOLD, a strong correlation pattern specific in L2/3 was detected for trials with negative BOLD in adjacent regions, which indicated brain state-dependent laminar-fMRI responses based on corticocortical interaction. Also, in resting-state (rs-) fMRI study, robust lag time differences in L2/3, 4, and 5 across multiple cortices represented the low-frequency rs-fMRI signal propagation from caudal to rostral slices. In summary, our study provided a unique laminar fMRI mapping scheme to better characterize trial-specific intra- and inter-laminar functional connectivity in evoked and resting-state MS-LS.

The impact of boarding schools on the development of cognitive and non-cognitive abilities in adolescents.

BACKGROUND: Since China adopted a policy to eliminate rural learning centers, boarding has become an important feature of the current rural student community. However, there is a lack of consensus on the impact of boarding schools on students' cognitive and non-cognitive development. This study investigates the effect of boarding schools on the development of cognitive and non-cognitive abilities of junior high school students in rural northwest China. METHODS: Using a sample of 5,660 seventh-grade students from 160 rural junior high schools across 19 counties, we identify a causal relationship between boarding and student abilities with the instrumental variables (IV) approach. RESULTS: The results suggest that boarding positively influences memory and attention, while it has no significant effect on other cognitive abilities such as reasoning, transcription speed, and accuracy. Furthermore, we find no significant association between boarding and the development of non-cognitive skills. CONCLUSIONS: Given the widespread prevalence of boarding schools in rural regions, our study highlights the growing importance of improving school management to promote the development of students' cognitive abilities and integrating the development of non-cognitive or social-emotional abilities into students' daily routines.

Genetic Evolution of Hepatitis E Virus.

Comparative analysis of the genomic sequences of multiple hepatitis E virus (HEV) isolates has revealed extensive genomic diversity among them. Recently, a variety of genetically distinct HEV variants have also been isolated and identified from large numbers of animal species, including birds, rabbits, rats, ferrets, bats, cutthroat trout, and camels, among others. Furthermore, it has been reported that recombination in HEV genomes takes place in animals and in human patients. Also, chronic HEV infection in immunocompromised individuals has revealed the presence of viral strains carrying insertions from human genes. This paper reviews current knowledge on the genomic variability and evolution of HEV.

Indexing brain state-dependent pupil dynamics with simultaneous fMRI and optical fiber calcium recording.

Pupillometry, a noninvasive measure of arousal, complements human functional MRI (fMRI) to detect periods of variable cognitive processing and identify networks that relate to particular attentional states. Even under anesthesia, pupil dynamics correlate with brain-state fluctuations, and extended dilations mark the transition to more arousable states. However, cross-scale neuronal activation patterns are seldom linked to brain state-dependent pupil dynamics. Here, we complemented resting-state fMRI in rats with cortical calcium recording (GCaMP-mediated) and pupillometry to tackle the linkage between brain-state changes and neural dynamics across different scales. This multimodal platform allowed us to identify a global brain network that covaried with pupil size, which served to generate an index indicative of the brain-state fluctuation during anesthesia. Besides, a specific correlation pattern was detected in the brainstem, at a location consistent with noradrenergic cell group 5 (A5), which appeared to be dependent on the coupling between different frequencies of cortical activity, possibly further indicating particular brain-state dynamics. The multimodal fMRI combining concurrent calcium recordings and pupillometry enables tracking brain state-dependent pupil dynamics and identifying unique cross-scale neuronal dynamic patterns under anesthesia.

Vitamin D receptor inhibits EMT via regulation of the epithelial mitochondrial function in intestinal fibrosis.

We previously showed that the vitamin D receptor (VDR) plays a crucial role in acute inflammatory bowel disease and that intestinal fibrosis is a common complication of Crohn's disease (CD). Epithelial-mesenchymal transition (EMT) is an important hallmark of fibrogenesis through which epithelial cells lose their epithelial phenotype and transform into mesenchymal cells. It is known that the VDR plays an essential role in epithelial integrity and mitochondrial function, but its role in intestinal fibrosis remains unknown. Here, we investigated whether the VDR is involved in epithelial mitochondrial dysfunction that results in EMT in intestinal fibrosis. Using human CD samples, intestine-specific VDR-KO mice, and fibroblast cellular models, we showed that the expression of the VDR was significantly lower in intestinal stenotic areas than in nonstenotic areas in patients with chronic CD. Genetic deletion of the VDR in the intestinal epithelium exacerbated intestinal fibrosis in mice administered with dextran sulfate sodium or 2,4,6-trinitrobenzene sulfonic acid, two experimental colitis inducers. In addition, we found that vitamin D dietary intervention regulated intestinal fibrosis by modulating the intestinal expression of the VDR. Mechanistically, knocking down the VDR in both CCD-18Co cells and human primary colonic fibroblasts promoted fibroblast activation, whereas VDR overexpression or VDR agonist administration inhibited fibroblast activation. Further analysis illustrated that the VDR inhibited EMT in the HT29 cell model and that mitochondrial dysfunction mediated epithelial integrity and barrier function in VDR-deficient epithelial cells. Together, our data for the first time demonstrate that VDR activation alleviates intestinal fibrosis by inhibiting fibroblast activation and epithelial mitochondria-mediated EMT.

Focal fMRI signal enhancement with implantable inductively coupled detectors.

Despite extensive efforts to increase the signal-to-noise ratio (SNR) of fMRI images for brain-wide mapping, technical advances of focal brain signal enhancement are lacking, in particular, for animal brain imaging. Emerging studies have combined fMRI with fiber optic-based optogenetics to decipher circuit-specific neuromodulation from meso to macroscales. High-resolution fMRI is needed to integrate hemodynamic responses into cross-scale functional dynamics, but the SNR remains a limiting factor given the complex implantation setup of animal brains. Here, we developed a multimodal fMRI imaging platform with an implanted inductive coil detector. This detector boosts the tSNR of MRI images, showing a 2-3-fold sensitivity gain over conventional coil configuration. In contrast to the cryoprobe or array coils with limited spaces for implanted brain interface, this setup offers a unique advantage to study brain circuit connectivity with optogenetic stimulation and can be further extended to other multimodal fMRI mapping schemes.

The DEAD-box helicase DDX3x ameliorates non-alcoholic fatty liver disease via mTORC1 signalling pathway.

BACKGROUND & AIMS: The DEAD (Asp-Glu-Ala-Asp)-box helicase family member DDX3x has been proven to involve in hepatic lipid disruption during HCV infection. However, the role of DDX3x in non-alcoholic fatty liver disease (NAFLD), in which lipid homeostasis is severely disrupted, remains unclear. Here, we aimed to illustrate the potential role of DDX3x in NAFLD. METHODS: DDX3x protein levels were evaluated in NAFLD patients and NAFLD models via immunohistochemistry or western blotting. In vivo ubiquitin assay was performed to identify the ubiquitination levels of DDX3x in the progression of steatosis. DDX3x protein levels in mice livers were manipulated by adeno-associated virus-containing DDX3x short hairpin RNA or DDX3x overexpression plasmid. Hepatic or serum triglyceride and total cholesterol were evaluated and hepatic steatosis was confirmed by haematoxylin and eosin staining and oil red o staining. Western blotting was performed to identify the underlying mechanisms of DDX3x involving in the progression of NAFLD. RESULTS: DDX3x protein levels were significantly decreased in NAFLD patients and NAFLD models. DDX3x protein might be degraded via ubiquitin-proteasome system in the progression of steatosis. Knockdown of hepatic DDX3x exacerbated HFD-induced hepatic steatosis in mice, while overexpression of hepatic DDX3x alleviated HFD-induced hepatic steatosis in mice. Further explorative experiments revealed that knockdown of DDX3x could lead to the overactivation of mTORC1 signalling pathway which exacerbates NAFLD. CONCLUSIONS: DDX3x involved in the progression of NAFLD via affecting the mTORC1 signalling pathway. DDX3x might be a potential target for NAFLD treatment.

Research on Aviation Safety Prediction Based on Variable Selection and LSTM.

Accurate prediction of aviation safety levels is significant for the efficient early warning and prevention of incidents. However, the causal mechanism and temporal character of aviation accidents are complex and not fully understood, which increases the operation cost of accurate aviation safety prediction. This paper adopts an innovative statistical method involving a least absolute shrinkage and selection operator (LASSO) and long short-term memory (LSTM). We compiled and calculated 138 monthly aviation insecure events collected from the Aviation Safety Reporting System (ASRS) and took minor accidents as the predictor. Firstly, this paper introduced the group variables and the weight matrix into LASSO to realize the adaptive variable selection. Furthermore, it took the selected variable into multistep stacked LSTM (MSSLSTM) to predict the monthly accidents in 2020. Finally, the proposed method was compared with multiple existing variable selection and prediction methods. The results demonstrate that the RMSE (root mean square error) of the MSSLSTM is reduced by 41.98%, compared with the original model; on the other hand, the key variable selected by the adaptive spare group lasso (ADSGL) can reduce the elapsed time by 42.67% (13 s). This shows that aviation safety prediction based on ADSGL and MSSLSTM can improve the prediction efficiency of the model while keeping excellent generalization ability and robustness.

Visual Size Processing in Early Visual Cortex Follows Lateral Occipital Cortex Involvement.

Neural activation in the early visual cortex (EVC) reflects the perceived rather than retinal size of stimuli, suggesting that feedback possibly from extrastriate regions modulates retinal size information in EVC. Meanwhile, the lateral occipital cortex (LOC) has been suggested to be critically involved in object size processing. To test for the potential contributions of feedback modulations on size representations in EVC, we investigated the dynamics of relevant processes using transcranial magnetic stimulation (TMS). Specifically, we briefly disrupted the neural activity of EVC and LOC at early, intermediate, and late time windows while participants performed size judgment tasks in either an illusory or neutral context. TMS over EVC and LOC allowed determining whether these two brain regions are relevant for generating phenomenological size impressions. Furthermore, the temporal order of TMS effects allowed inferences on the dynamics of information exchange between the two areas. Particularly, if feedback signals from LOC to EVC are crucial for generating altered size representations in EVC, then TMS effects over EVC should be observed simultaneously or later than the effects following LOC stimulation. The data from 20 humans (13 females) revealed that TMS over both EVC and LOC impaired illusory size perception. However, the strongest effects of TMS applied over EVC occurred later than those of LOC, supporting a functionally relevant feedback modulation from LOC to EVC for scaling size information. Our results suggest that context integration and the concomitant change of perceived size require LOC and result in modulating representations in EVC via recurrent processing.SIGNIFICANCE STATEMENT How we perceive an object's size is not entirely determined by its physical size or the size of its retinal representation but also the spatial context. Using transcranial magnetic stimulation, we investigated the role of the early visual cortex (EVC) and the higher-level visual area, lateral occipital cortex (LOC), known to be critically involved in object processing, in transforming an initial retinal representation into one that reflects perceived size. Transcranial magnetic stimulation altered size perception earlier over LOC compared with EVC, suggesting that context integration and the concomitant change in perceived size representations in EVC rely on feedback from LOC.

Vitamin D receptor targets hepatocyte nuclear factor 4α and mediates protective effects of vitamin D in nonalcoholic fatty liver disease.

Epidemiological studies have suggested a link between vitamin D deficiency and increased risk for nonalcoholic fatty liver disease (NAFLD); however, the underlying mechanisms have remained unclear. Here, using both clinical samples and experimental rodent models along with several biochemical approaches, we explored the specific effects and mechanisms of vitamin D deficiency in NAFLD pathology. Serum vitamin D levels were significantly lower in individuals with NAFLD and in high-fat diet (HFD)-fed mice than in healthy controls and chow-fed mice, respectively. Vitamin D supplementation ameliorated HFD-induced hepatic steatosis and insulin resistance in mice. Hepatic expression of vitamin D receptor (VDR) was up-regulated in three models of NAFLD, including HFD-fed mice, methionine/choline-deficient diet (MCD)-fed mice, and genetically obese (ob/ob) mice. Liver-specific VDR deletion significantly exacerbated HFD- or MCD-induced hepatic steatosis and insulin resistance and also diminished the protective effect of vitamin D supplementation on NAFLD. Mechanistic experiments revealed that VDR interacted with hepatocyte nuclear factor 4 α (HNF4α) and that overexpression of HNF4α improved HFD-induced NAFLD and metabolic abnormalities in liver-specific VDR-knockout mice. These results suggest that vitamin D ameliorates NAFLD and metabolic abnormalities by activating hepatic VDR, leading to its interaction with HNF4α. Our findings highlight a potential value of using vitamin D for preventing and managing NAFLD by targeting VDR.

Deficiency in the anti-apoptotic protein DJ-1 promotes intestinal epithelial cell apoptosis and aggravates inflammatory bowel disease via p53.

Parkinson disease autosomal recessive, early onset 7 (PARK7 or DJ-1) is involved in multiple physiological processes and exerts anti-apoptotic effects on multiple cell types. Increased intestinal epithelial cell (IEC) apoptosis and excessive activation of the p53 signaling pathway is a hallmark of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). However, whether DJ-1 plays a role in colitis is unclear. To determine whether DJ-1 deficiency is involved in the p53 activation that results in IEC apoptosis in colitis, here we performed immunostaining, real-time PCR, and immunoblotting analyses to assess DJ-1 expression in human UC and CD samples. In the inflamed intestines of individuals with IBD, DJ-1 expression was decreased and negatively correlated with p53 expression. DJ-1 deficiency significantly aggravated colitis, evidenced by increased intestinal inflammation and exacerbated IEC apoptosis. Moreover, DJ-1 directly interacted with p53, and reduced DJ-1 levels increased p53 levels both in vivo and in vitro and were associated with decreased p53 degradation via the lysosomal pathway. We also induced experimental colitis with dextran sulfate sodium in mice and found that compared with DJ-1-/- mice, DJ-1-/-p53-/- mice have reduced apoptosis and inflammation and increased epithelial barrier integrity. Furthermore, pharmacological inhibition of p53 relieved inflammation in the DJ-1-/- mice. In conclusion, reduced DJ-1 expression promotes inflammation and IEC apoptosis via p53 in colitis, suggesting that the modulation of DJ-1 expression may be a potential therapeutic strategy for managing colitis.

GCSF deficiency attenuates nonalcoholic fatty liver disease through regulating GCSFR-SOCS3-JAK-STAT3 pathway and immune cells infiltration.

Granulocyte colony stimulating factor (GCSF) is a cytokine with immunomodulation effects. However, little is known about its role in metabolic diseases. In the current study, we aimed to explore the role of GCSF in nonalcoholic fatty liver disease (NAFLD). Male GCSF-/- mice were used to investigate the function of GCSF in vivo after high-fat diet (HFD). Primary hepatocytes were used for evaluating the function of GCSF in vitro. Liver immune cells were isolated and analyzed by flow cytometry. Our results showed that GCSF administration significantly increased serum triglyceride (TG) levels in patients. Circulating GCSF was markedly elevated in HFD-fed mice. GCSF-/- mice exhibited alleviated HFD-induced obesity, insulin resistance, and hepatic steatosis. Extra administration of GCSF significantly aggravated palmitic acid (PA)-induced lipid accumulation in primary hepatocytes. Mechanically, GCSF could bind to granulocyte colony stimulating factor receptor (GCSFR) and regulate suppressors of cytokine signaling 3, Janus kinase, signal transducer and activator of transcription 3 (SOCS3-JAK-STAT3) pathway. GCSF also enhanced hepatic neutrophils and macrophages infiltration, thereby modulating NAFLD. These findings suggest that GCSF plays an important regulatory role in NAFLD and may be a potential therapeutic target for NAFLD.NEW & NOTEWORTHY We found GCSF was involved in lipid metabolism and NAFLD development. GCSF administration increased serum triglyceride levels in patients. GCSF deficiency alleviated HFD-induced insulin resistance and hepatic steatosis in mice. GCSF could directly act on hepatocytes through GCSFR-SOCS3-JAK-STAT3 pathway, and regulate the infiltration of immune cells into the liver to indirectly modulate NAFLD. Our finding indicates that GCSF may provide new strategies for the treatment of NAFLD.

Feedback from lateral occipital cortex to V1/V2 triggers object completion: Evidence from functional magnetic resonance imaging and dynamic causal modeling.

Illusory figures demonstrate the visual system's ability to integrate disparate parts into coherent wholes. We probed this object integration process by either presenting an integrated diamond shape or a comparable ungrouped configuration that did not render a complete object. Two tasks were used that either required localization of a target dot (relative to the presented configuration) or discrimination of the dot's luminance. The results showed that only when the configuration was task relevant (in the localization task), performance benefited from the presentation of an integrated object. Concurrent functional magnetic resonance imaging was performed and analyzed using dynamic causal modeling to investigate the (causal) relationship between regions that are associated with illusory figure completion. We found object-specific feedback connections between the lateral occipital cortex (LOC) and early visual cortex (V1/V2). These modulatory connections persisted across task demands and hemispheres. Our results thus provide direct evidence that interactions between mid-level and early visual processing regions engage in illusory figure perception. These data suggest that LOC first integrates inputs from multiple neurons in lower-level cortices, generating a global shape representation while more fine-graded object details are then determined via feedback to early visual areas, independently of the current task demands.

Characterization of Lysozyme-Like Effector TseP Reveals the Dependence of Type VI Secretion System (T6SS) Secretion on Effectors in Aeromonas dhakensis Strain SSU.

The type VI secretion system (T6SS) is a widespread weapon employed by Gram-negative bacteria for interspecies interaction in complex communities. Analogous to a contractile phage tail, the double-tubular T6SS injects toxic effectors into prokaryotic and eukaryotic neighboring cells. Although effectors dictate T6SS functions, their identities remain elusive in many pathogens. Here, we report the lysozyme-like effector TseP in Aeromonas dhakensis, a waterborne pathogen that can cause severe gastroenteritis and systemic infection. Using secretion, competition, and enzymatic assays, we demonstrate that TseP is a T6SS-dependent effector with cell wall-lysing activities, and TsiP is its cognate immunity protein. Triple deletion of tseP and two known effector genes, tseI and tseC, abolished T6SS-mediated secretion, while complementation with any single effector gene partially restored bacterial killing and Hcp secretion. In contrast to whole-gene deletions, the triple-effector inactivation in the 3effc mutant abolished antibacterial killing but not T6SS secretion. We further demonstrate that the 3effc mutation abolished T6SS-mediated toxicity of SSU to Dictyostelium discoideum amoebae, suggesting that the T6SS physical puncture is nontoxic to eukaryotic cells. These data highlight not only the necessity of possessing functionally diverse effectors for survival in multispecies communities but also that effector inactivation would be an efficient strategy to detoxify the T6SS while preserving its delivery efficiency, converting the T6SS to a platform for protein delivery to a variety of recipient cells. IMPORTANCE Delivery of cargo proteins via protein secretion systems has been shown to be a promising tool in various applications. However, secretion systems are often used by pathogens to cause disease. Thus, strategies are needed to detoxify secretion systems while preserving their efficiency. The T6SS can translocate proteins through physical puncture of target cells without specific surface receptors and can target a broad range of recipients. In this study, we identified a cell wall-lysing effector, and by inactivating it and the other two known effectors, we have built a detoxified T6SS-active strain that may be used for protein delivery to prokaryotic and eukaryotic recipient cells.

Spontaneous Adsorption-Induced Salvinia-like Micropillars with High Adhesion.

Superhydrophobic surfaces with high adhesion provide high potential for underwater applications. Inspired by Salvinia leaf, here, we have reported a simple method for fabricating adhesive Salvinia-like micropillars via photolithography and spontaneous adsorption of organic molecules from the atmosphere. With continuous hydrocarbon adsorption on sputtered cerium dioxide (CeO2) films, the surface gradually evolved and eventually became chemically heterogeneous. Huge wetting contrast from superhydrophilic to superhydrophobic over exposure time was observed; meanwhile, the wetting mode changed from the Wenzel (W) state to Cassie-Baxter (C-B) state. As a result, hydrophobic hydrocarbons (C-C/C-H) and trapped air between adjacent pillars contributed to the high apparent contact angle (CA), while the hydrophilic domains of C-O/O═C-O and CeO2 on the top layer made the surface highly adhesive with water droplets. In comparison with traditional fluorinated superhydrophobic surfaces, CeO2-coated surfaces showed high adhesive force with water droplets and can be used as a "mechanical hand" for water droplet transport. The adsorption-induced Salvinia-like micropillars with high adhesion may find many other droplet-based applications in microfluidic fields.

Tracking the completion of parts into whole objects: Retinotopic activation in response to illusory figures in the lateral occipital complex.

Illusory figures demonstrate the visual system's ability to integrate separate parts into coherent, whole objects. The present study was performed to track the neuronal object construction process in human observers, by incrementally manipulating the grouping strength within a given configuration until the emergence of a whole-object representation. Two tasks were employed: First, in the spatial localization task, object completion could facilitate performance and was task-relevant, whereas it was irrelevant in the second, luminance discrimination task. Concurrent functional magnetic resonance imaging (fMRI) used spatial localizers to locate brain regions representing task-critical illusory-figure parts to investigate whether the step-wise object construction process would modulate neural activity in these localized brain regions. The results revealed that both V1 and the lateral occipital complex (LOC, with sub-regions LO1 and LO2) were involved in Kanizsa figure processing. However, completion-specific activations were found predominantly in LOC, where neural activity exhibited a modulation in accord with the configuration's grouping strength, whether or not the configuration was relevant to performing the task at hand. Moreover, right LOC activations were confined to LO2 and responded primarily to surface and shape completions, whereas left LOC exhibited activations in both LO1 and LO2 and was related to encoding shape structures with more detail. Together, these results demonstrate that various grouping properties within a visual scene are integrated automatically in LOC, with sub-regions located in different hemispheres specializing in the component sub-processes that render completed objects.

Identification of ireA, 0007, 0008, and 2235 as TonB-dependent receptors in the avian pathogenic Escherichia coli strain DE205B.

Avian pathogenic Escherichia coli (APEC), a pathotype of extraintestinal pathogenic E. coli, causes one of the most serious infectious diseases of poultry and shares some common virulence genes with neonatal meningitis-associated E. coli. TonB-dependent receptors (TBDRs) are ubiquitous outer membrane ß-barrel proteins; they play an important role in the recognition of siderophores during iron uptake. Here, in the APEC strain DE205B, we investigated the role of four putative TBDRs-ireA, 0007, 0008, and 2235-in iron uptake. Glutathione-S-transferase pulldown assays indicated that the proteins encoded by these genes directly interact with TonB. Moreover, the expression levels of all four genes were significantly upregulated under iron-depleted conditions compared with iron-rich conditions. The expression levels of several iron uptake-related genes were significantly increased in the ireA, 0007, 0008, and 2235 deletion strains, with the upregulation being the most prominent in the ireA deletion mutant. Furthermore, iron uptake by the ireA deletion strain was significantly increased compared to that by the wild-type strain. Moreover, a tonB mutant strain was constructed to study the effect of tonB deletion on the TBDRs. We found that regardless of the presence of tonB, the expression levels of the genes encoding the four TBDRs were regulated by fur. In conclusion, our findings indicated that ireA, 0007, 0008, and 2235 indeed encode TBDRs, with ireA having the most important role in iron uptake. These results should help future studies explore the mechanisms underlying the TonB-dependent iron uptake pathway.

PPARα regulates tumor cell proliferation and senescence via a novel target gene carnitine palmitoyltransferase 1C.

Carnitine palmitoyltransferase 1C (CPT1C), an enzyme located in the outer mitochondria membrane, has a crucial role in fatty acid transport and oxidation. It is also involved in cell proliferation and is a potential driver for cancer cell senescence. However, its upstream regulatory mechanism is unknown. Peroxisome proliferator activated receptor α (PPARα) is a ligand-activated transcription factor that regulates lipid metabolism and tumor progression. The current study aimed to elucidate whether and how PPARα regulates CPT1C and then affects cancer cell proliferation and senescence. Here, for the first time we report that PPARα directly activated CPT1C transcription and CPT1C was a novel target gene of PPARα, as revealed by dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. Moreover, regulation of CPT1C by PPARα was p53-independent. We further confirmed that depletion of PPARα resulted in low CPT1C expression and then inhibited proliferation and induced senescence of MDA-MB-231 and PANC-1 tumor cell lines in a CPT1C-dependent manner, while forced PPARα overexpression promoted cell proliferation and reversed cellular senescence. Taken together, these results indicate that CPT1C is a novel PPARα target gene that regulates cancer cell proliferation and senescence. The PPARα-CPT1C axis may be a new target for the intervention of cancer cellular proliferation and senescence.