An SREBP-Responsive microRNA Operon Contributes to a Regulatory Loop for Intracellular Lipid Homeostasis

SummarySterol regulatory element-binding proteins (SREBPs) have evolved as a focal point for linking lipid synthesis with other pathways that regulate cell growth and survival. Here, we have uncovered a polycistrionic microRNA (miRNA) locus that is activated directly by SREBP-2. Two of the encoded miRNAs, miR-182 and miR-96, negatively regulate the expression of Fbxw7 and Insig-2, respectively, and both are known to negatively affect nuclear SREBP accumulation. Direct manipulation of this miRNA pathway alters nuclear SREBP levels and endogenous lipid synthesis. Thus, we have uncovered a mechanism for the regulation of intracellular lipid metabolism mediated by the concerted action of a pair of miRNAs that are expressed from the same SREBP-2-regulated miRNA locus, and each targets a different protein of the multistep pathway that regulates SREBP function. These studies reveal an miRNA “operon” analogous to the classic model for genetic control in bacterial regulatory systems

Antitumorigenic effect of atmospheric-pressure dielectric barrier discharge on human colorectal cancer cells via regulation of Sp1 transcription factor

Human colorectal cancer cell lines (HT29 and HCT116) were exposed to dielectric barrier discharge (DBD) plasma at atmospheric pressure to investigate the anticancer capacity of the plasma. The dose- and time-dependent effects of DBDP on cell viability, regulation of transcription factor Sp1, cell-cycle analysis, and colony formation were investigated by means of MTS assay, DAPI staining, propidium iodide staining, annexin V-FITC staining, Western blot analysis, RT-PCR analysis, fluorescence microscopy, and anchorage-independent cell transformation assay. By increasing the duration of plasma dose times, significant reductions in the levels of both Sp1 protein and Sp1 mRNA were observed in both cell lines. Also, expression of negative regulators related to the cell cycle (such as p53, p21, and p27) was increased and of the positive regulator cyclin D1 was decreased, indicating that the plasma treatment led to apoptosis and cell-cycle arrest. In addition, the sizes and quantities of colony formation were significantly suppressed even though two cancer promoters, such as TPA and epidermal growth factor, accompanied the plasma treatment. Thus, plasma treatment inhibited cell viability and colony formation by suppressing Sp1, which induced apoptosis and cell-cycle arrest in these two human colorectal cancer cell lines.1

Meteorological characteristics and assessment of the effect of local emissions during high PM10 concentration in the Seoul Metropolitan Area

In this study, we investigate the meteorological characteristics and the effect of local emissions during high PM10 concentrations in the Seoul Metropolitan Area (SMA) by utilizing data from a high-resolution urban meteorological observation system network (UMS-Seoul) and The Air Pollution Model (TAPM). For a detailed analysis, days with PM10 concentrations higher than 80 ??g m-3 for daily average PM10 concentration (classified as unhealthy by the Korean Ministry of Environment) in the Seoul Metropolitan Area (SMA) were classified into 3 Cases. Case I was defined as when the prevailing effect was from outside the SMA. Case II was defined as when the prevailing effect was a local effect with outside. Case III was defined as when the prevailing effect was local. Overall, high PM10 concentrations in the SMA mostly occurred under weak migratory anticyclone systems over the Korean Peninsula during warm temperatures. Prior to the PM10 concentration reaching the peak concentration, the pattern in each case was distinctive. After peak concentrations, however, the pattern for the 3 cases became less distinct. This study showed that nearly 50% of the high PM10 concentrations in the SMA occurred in spring and were governed by the conditions for Case II more than these for Cases I and III. In spring, the main sources of the high PM10 concentrations in the SMA were local emissions due to the predominance of weak winds and local circulation. The simulation showed that the non-SMA emissions were about 63 to 73% contribution to the spring high PM10 concentrations in the SMA. Specifically, local point sources including industrial combustion, electric utility, incineration and cement production facilities scattered around the SMA and could account for PM10 concentrations more than 10 ??g m-3 in the SMA

Observation of the in-plane magnetic field-induced phase transitions in FeSe

We investigate the thermodynamic properties of FeSe under the in-plane magnetic fields using torque magnetometry, specific heat, magnetocaloric measurements. Below the upper critical field Hc2, we observed the field-induced anomalies at H1 ~ 15 T and H2 ~ 22 T near H//ab and below a characteristic temperature T* ~ 2 K. The transition magnetic fields H1 and H2 exhibit negligible dependence on both temperature and field orientation. This contrasts with the strong temperature and angle dependence of Hc2, suggesting that these anomalies are attributed to the field-induced phase transitions, originating from the inherent spin-density-wave instability of quasiparticles near the superconducting gap minima or possible Flude-Ferrell-Larkin-Ovchinnikov state in the highly spin-polarized Fermi surfaces. Our observations imply that FeSe, an atypical multiband superconductor with extremely small Fermi energies, represents a unique model system for stabilizing unusual superconducting orders beyond the Pauli limit.Comment: 8 pages, 4 figures, submitte

Evaluation of the Efficacy and Cross-Protectivity of Recent Human and Swine Vaccines against the Pandemic (H1N1) 2009 Virus Infection

The current pandemic (H1N1) 2009 virus remains transmissible among humans worldwide with cases of reverse zoonosis, providing opportunities to produce more pathogenic variants which could pose greater human health concerns. To investigate whether recent seasonal human or swine H1N1 vaccines could induce cross-reactive immune responses against infection with the pandemic (H1N1) 2009 virus, mice, ferrets or mini-pigs were administered with various regimens (once or twice) and antigen content (1.77, 3.5 or 7.5 µg HA) of a-Brsibane/59/07, a-CAN01/04 or RgCA/04/09xPR8 vaccine. Receipt of a-CAN01/04 (2-doses) but not a-Brisbane/59/07 induced detectable but modest (20–40 units) cross-reactive serum antibody against CA/04/09 by hemagglutinin inhibition (HI) assays in mice. Only double administration (7.5 µg HA) of both vaccine in ferrets could elicit cross-reactivity (30–60 HI titers). Similar antigen content of a-CAN01/04 in mini-pigs also caused a modest ∼30 HI titers (twice vaccinated). However, vaccine-induced antibody titers could not suppress active virus replication in the lungs (mice) or virus shedding (ferrets and pigs) of immunized hosts intranasally challenged with CA/04/09. Furthermore, neither ferrets nor swine could abrogate aerosol transmission of the virus into naïve contact animals. Altogether, these results suggest that neither recent human nor animal H1N1 vaccine could provide complete protectivity in all animal models. Thus, this study warrants the need for strain-specific vaccines that could yield the optimal protection desired for humans and/or animals

Tropical Cyclones and Climate Change

Trabajo presentado en: 10th International Worskshop Cyclones Tropicales, celebrado del 5 al 9 de diciembre de 2022 en Bali, Indonesia.A substantial number of studies have been published since the IWTC-9 in 2018, improving our understanding of the effect of climate change on tropical cyclones (TCs) and associated hazards and risks. They reinforced the robustness of increases in TC intensity and associated TC hazards and risks due to anthropogenic climate change. New modeling and observational studies suggested the potential influence of anthropogenic climate forcings, including greenhouse gases and aerosols, on global and regional TC activity at the decadal and century time scale. However, there is still substantial uncertainty owing to model uncertainty in simulating historical TC decadal variability in the Atlantic and owing to limitations of observed TC records. The projected future change in the global number of TCs has become more uncertain since IWTC-9 due to projected increases in TC frequency by a few climate models. A new paradigm, TC seeds, has been proposed, and there is currently a debate on whether seeds can help explain the physical mechanism behind the projected changes in global TC frequency. New studies also highlighted the importance of large-scale environmental fields on TC activity, such as snow cover and air-sea interactions. Future projections on TC translation speed and Medicanes are new additional focus topics in our report. Recommendations and future research are proposed relevant to the remaining scientific questions and assisting policymakers

Impact Comparison of Synoptic Meteorology and Nationwide/local Emissions on the Seoul Metropolitan Area during High PM Multi-event and Non-event Days

Meteorology and emissions play very important roles in the concentrations of air pollutants during severe haze/smog periods. This study compares the impacts of synoptic meteorology and nationwide/local emissions during high PM10 multi-event and non-event days in the Seoul Metropolitan Area (SMA). The multi-event and non-event cases were selected based on daily mean PM10 concentrations in Seoul from January 2014 to March 2019. The multi-event cases in spring and winter were closely associated with weak synoptic winds, while that in autumn was due to the strong winds at the rear side of a strong cold front, which induced the Asian dust event in northeastern China and Korea. The multi-event case in spring was found to be mainly due to series of migratory anticyclones, while winter case was due to the stagnant system after northerly winds. The surrounding low pressure systems as well as high pressure systems could be important to determine whether the synoptic systems would be stagnant or not. The fractional contributions of SMA emissions to the mean PM10 and PM2.5 concentrations were 24%-35% and 22%-35% for the multi-event cases, respectively. The contributions to the maximum PM10 and PM2.5 concentrations were larger than those to the mean concentrations by 16%-23% and 19%-26% for the multi-event cases, respectively

Stereotactic body radiotherapy for hepatocellular carcinoma: meta-analysis and International Stereotactic Radiosurgery Society practice guidelines

PURPOSE This systematic review and meta-analysis reports on outcomes and hepatic toxicity rates following stereotactic body radiotherapy (SBRT) for liver confined hepatocellular carcinoma (HCC), and presents consensus guidelines regarding appropriate patient management. METHODS AND MATERIALS Using the Preferred Reporting Items for Systemic Review and Meta-analyses guidelines, a systematic review was performed from articles reporting outcomes at ≥5 years published prior to October 2022 from the Embase, MEDLINE, Cochrane, and Scopus databases using the key words terms ("Stereotactic body radiotherapy" OR "SBRT" OR "SABR" OR "Stereotactic ablative radiotherapy") AND ("Hepatocellular carcinoma" OR "HCC"). An aggregated data (AD) meta-analysis was conducted to assess overall survival (OS) and local control (LC) using weighted random effects models. In addition, an individual patient data (IPD) analysis incorporating data from 6 institutions was conducted as its own subgroup analyses. RESULTS Seventeen observational studies, comprising 1889 HCC patients treated with ≤9 SBRT fractions, between 2003 and 2019, were included in the AD meta-analysis. The 3- and 5- year OS rates after SBRT were 57% (95% confidence interval [CI], 47-66%) and 40% (95% CI, 29-51%). The 3- and 5- year LC rates after SBRT were 84% (95% CI, 77-90%) and 82% (95% CI, 74-88%), respectively. Tumor size was the only prognostic factor for LC. Tumor size and region were significantly associated with OS. Five-year LC and OS rates of 79% (95% CI, 0.74-0.84) and 25% (95% CI, 0.20-0.30), respectively, were observed in the IPD analyses. Factors prognostic for improved OS were tumor size <3 cm, eastern region, Child-Pugh score ≤B7, and the Barcelona Clinic Liver Cancer stage of 0 and A. The incidence of severe hepatic toxicity varied according to the criteria applied. CONCLUSIONS SBRT is an effective treatment modality for HCC patients with mature follow up. Clinical practice guidelines were developed on behalf of the XXXX

Invertebrate 7SK snRNAs

7SK RNA is a highly abundant noncoding RNA in mammalian cells whose function in transcriptional regulation has only recently been elucidated. Despite its highly conserved sequence throughout vertebrates, all attempts to discover 7SK RNA homologues in invertebrate species have failed so far. Here we report on a combined experimental and computational survey that succeeded in discovering 7SK RNAs in most of the major deuterostome clades and in two protostome phyla: mollusks and annelids. Despite major efforts, no candidates were found in any of the many available ecdysozoan genomes, however. The additional sequence data confirm the evolutionary conservation and hence functional importance of the previously described 3′ and 5′ stem-loop motifs, and provide evidence for a third, structurally well-conserved domain