Liver-Specific Deletion of Mouse CTCF Leads to Hepatic Steatosis via Augmented PPARγ Signaling

Background & Aims: The liver is the major organ for metabolizing lipids, and malfunction of the liver leads to various diseases. Nonalcoholic fatty liver disease is rapidly becoming a major health concern worldwide and is characterized by abnormal retention of excess lipids in the liver. CCCTC-binding factor (CTCF) is a highly conserved zinc finger protein that regulates higher-order chromatin organization and is involved in various gene regulation processes. Here, we sought to determine the physiological role of CTCF in hepatic lipid metabolism. Methods: We generated liver-specific, CTCF-ablated and/or CD36 whole-body knockout mice. Overexpression or knockdown of peroxisome proliferator-activated receptor (PPAR)γ in the liver was achieved using adenovirus. Mice were examined for development of hepatic steatosis and inflammation. RNA sequencing was performed to identify genes affected by CTCF depletion. Genome-wide occupancy of H3K27 acetylation, PPARγ, and CTCF were analyzed by chromatin immunoprecipitation sequencing. Genome-wide chromatin interactions were analyzed by in situ Hi-C. Results: Liver-specific, CTCF-deficient mice developed hepatic steatosis and inflammation when fed a standard chow diet. Global analysis of the transcriptome and enhancer landscape revealed that CTCF-depleted liver showed enhanced accumulation of PPARγ in the nucleus, which leads to increased expression of its downstream target genes, including fat storage-related gene CD36, which is involved in the lipid metabolic process. Hepatic steatosis developed in liver-specific, CTCF-deficient mice was ameliorated by repression of PPARγ via pharmacologic blockade or adenovirus-mediated knockdown, but hardly rescued by additional knockout of CD36. Conclusions: Our data indicate that liver-specific deletion of CTCF leads to hepatosteatosis through augmented PPARγ DNA-binding activity, which up-regulates its downstream target genes associated with the lipid metabolic process. © 2021 The Authors1

SoccerNet 2023 Challenges Results

peer reviewedThe SoccerNet 2023 challenges were the third annual video understanding challenges organized by the SoccerNet team. For this third edition, the challenges were composed of seven vision-based tasks split into three main themes. The first theme, broadcast video understanding, is composed of three high-level tasks related to describing events occurring in the video broadcasts: (1) action spotting, focusing on retrieving all timestamps related to global actions in soccer, (2) ball action spotting, focusing on retrieving all timestamps related to the soccer ball change of state, and (3) dense video captioning, focusing on describing the broadcast with natural language and anchored timestamps. The second theme, field understanding, relates to the single task of (4) camera calibration, focusing on retrieving the intrinsic and extrinsic camera parameters from images. The third and last theme, player understanding, is composed of three low-level tasks related to extracting information about the players: (5) re-identification, focusing on retrieving the same players across multiple views, (6) multiple object tracking, focusing on tracking players and the ball through unedited video streams, and (7) jersey number recognition, focusing on recognizing the jersey number of players from tracklets. Compared to the previous editions of the SoccerNet challenges, tasks (2-3-7) are novel, including new annotations and data, task (4) was enhanced with more data and annotations, and task (6) now focuses on end-to-end approaches. More information on the tasks, challenges, and leaderboards are available on https://www.soccer-net.org. Baselines and development kits can be found on https://github.com/SoccerNet

Effect of Docosahexaenoic Acid on Ca2+ Signaling Pathways in Cerulein-Treated Pancreatic Acinar Cells, Determined by RNA-Sequencing Analysis

Intracellular Ca2+ homeostasis is commonly disrupted in acute pancreatitis. Sustained Ca2+ release from internal stores in pancreatic acinar cells (PACs), mediated by inositol triphosphate receptor (IP3R) and the ryanodine receptor (RyR), plays a key role in the initiation and propagation of acute pancreatitis. Pancreatitis induced by cerulein, an analogue of cholecystokinin, causes premature activation of digestive enzymes and enhanced accumulation of cytokines and Ca2+ in the pancreas and, as such, it is a good model of acute pancreatitis. High concentrations of the omega-3 fatty acid docosahexaenoic acid (DHA) inhibit inflammatory signaling pathways and cytokine expression in PACs treated with cerulein. In the present study, we determined the effect of DHA on key regulators of Ca2+ signaling in cerulein-treated pancreatic acinar AR42 J cells. The results of RNA-Sequencing (RNA-Seq) analysis showed that cerulein up-regulates the expression of IP3R1 and RyR2 genes, and that pretreatment with DHA blocks these effects. The results of real-time PCR confirmed that DHA inhibits cerulein-induced IP3R1 and RyR2 gene expression, and demonstrated that DHA pre-treatment decreases the expression of the Relb gene, which encodes a component of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcriptional activator complex, and the c-fos gene, which encodes a component of activator protein-1 (AP-1) transcriptional activator complex. Taken together, DHA inhibits mRNA expression of IP3R1, RyR2, Relb, and c-fos, which is related to Ca2+ network in cerulein-stimulated PACs

Immunomodulation of HDAC Inhibitor Entinostat Potentiates the Anticancer Effects of Radiation and PD-1 Blockade in the Murine Lewis Lung Carcinoma Model

Although the combination of radiotherapy and immunotherapy has proven to be effective in lung cancer treatment, it may not be sufficient to fully activate the antitumor immune response. Here, we investigated whether entinostat, a histone deacetylase inhibitor, could improve the efficacy of radiotherapy and anti-PD-1 in a murine syngeneic LL/2 tumor model. A total of 12 Gy of X-rays administered in two fractions significantly delayed tumor growth in mice, which was further enhanced by oral entinostat administration. Flow cytometry-aided immune cell profiling revealed that entinostat increased radiation-induced infiltration of myeloid-derived suppressor cells and CD8+ T cells with decreased regulatory T-cells (Tregs). Transcriptomics-based immune phenotype prediction showed that entinostat potentiated radiation-activated pathways, such as JAK/STAT3/interferon-gamma (IFN-γ) and PD-1/PD-L1 signaling. Entinostat augmented the antitumor efficacy of radiation and anti-PD-1, which may be related to an increase in IFN-γ-producing CD8+ T-cells with a decrease in Treg cells. Comparative transcriptomic profiling predicted that entinostat increased the number of dendritic cells, B cells, and T cells in tumors treated with radiation and anti-PD-1 by inducing MHC-II genes. In conclusion, our findings provided insights into how entinostat improves the efficacy of ionizing radiation plus anti-PD-1 therapy and offered clues for developing new strategies for clinical trials

Restricted Channel Migration in 2D Multilayer ReS 2

International audienc

Data_Sheet_1_Prevalence and phylogenetic analysis of human enteric emerging viruses in porcine stool samples in the Republic of Korea.docx

Emerging infectious diseases (EID) in humans and animals are proving to be a serious health concern. This study investigated the prevalence of emerging or re-emerging human enteric viruses in porcine stools and swabs. Eleven enteric EID viruses were selected as target viruses for the current study and ranked based on their impact on public health and food safety: enterovirus (EV), hepatitis E virus, norovirus GI and GII, sapovirus (SaV), adenovirus (AdV), astrovirus, rotavirus, hepatitis A virus, aichivirus, and bocavirus. Using real-time RT-PCR or real-time PCR, EID viruses were detected in 129 (86.0%) of 150 samples. The most prevalent virus was EV, which was detected in 68.0% of samples, followed by AdV with a detection rate of 38.0%. In following sequencing and phylogenetic analyses, 33.0% (58/176) of the detected viruses were associated with human enteric EID viruses, including AdV-41, coxsackievirus-A2, echovirus-24, and SaV. Our results show that porcine stools frequently contain human enteric viruses, and that few porcine enteric viruses are genetically related to human enteric viruses. These findings suggest that enteric re-emerging or EID viruses could be zoonoses, and that continuous monitoring and further studies are needed to ensure an integrated “One Health” approach that aims to balance and optimize the health of humans, animals, and ecosystems.</p

Data_Sheet_2_Prevalence and phylogenetic analysis of human enteric emerging viruses in porcine stool samples in the Republic of Korea.xlsx

Emerging infectious diseases (EID) in humans and animals are proving to be a serious health concern. This study investigated the prevalence of emerging or re-emerging human enteric viruses in porcine stools and swabs. Eleven enteric EID viruses were selected as target viruses for the current study and ranked based on their impact on public health and food safety: enterovirus (EV), hepatitis E virus, norovirus GI and GII, sapovirus (SaV), adenovirus (AdV), astrovirus, rotavirus, hepatitis A virus, aichivirus, and bocavirus. Using real-time RT-PCR or real-time PCR, EID viruses were detected in 129 (86.0%) of 150 samples. The most prevalent virus was EV, which was detected in 68.0% of samples, followed by AdV with a detection rate of 38.0%. In following sequencing and phylogenetic analyses, 33.0% (58/176) of the detected viruses were associated with human enteric EID viruses, including AdV-41, coxsackievirus-A2, echovirus-24, and SaV. Our results show that porcine stools frequently contain human enteric viruses, and that few porcine enteric viruses are genetically related to human enteric viruses. These findings suggest that enteric re-emerging or EID viruses could be zoonoses, and that continuous monitoring and further studies are needed to ensure an integrated “One Health” approach that aims to balance and optimize the health of humans, animals, and ecosystems.</p

Hidden surface channel in two-dimensional multilayers

International audienceAbstract Numerous carrier scatterers, such as atomic defects, fixed oxide charges, impurities, chemical residues, and undesired surface adsorbates, including oxygen and water molecules, strongly degrade the carrier mobility of atomically thin two-dimensional (2D) materials. However, the effect of surface adsorbates and surface oxidation on the carrier density profile along the thickness of 2D multilayers is not well known, particularly for a substantial interruption in the formation of the top-surface channel. Here, we uncover a hidden surface channel in p-type black phosphorus and n-type rhenium disulfide multilayers originating from undesired ambient adsorbates and surface oxides that not only populate hole density (or reduce electron density) but also suppress carrier mobility. The absence of a second peak in the transconductance curve under ambient conditions indicates the disappearance of the top-surface channel inside the 2D multilayers, which is a possible indicator for the cleanliness of the top surface and can be used in gas sensor applications. Moreover, the negligible variation in the drain bias polarity-dependent turn-on voltage for the bottom channel under ambient conditions validates the exclusive contribution of surface adsorbates to the formation of the top channel in 2D multilayers. Our results provide a novel insight into the distinct carrier transport in 2D optoelectronic devices and diverse sensors