Extreme weather events and the energy sector in 2021

In 2021, the energy sector was put at risk by extreme weather in many different ways: North America and Spain suffered heavy winter storms that led to the collapse of the electricity network; California specifically experienced heavy droughts and heatwave conditions, causing the operations of hydropower stations to halt; floods caused substantial damage to energy infrastructure in central Europe, Australia and China throughout the year, and unusual wind drought conditions decreased wind power production in the United Kingdom by almost 40% during summer. The total economic impacts of these extreme weather events are estimated at billions of USD. Here we review and assess in some detail the main extreme weather events that impacted the energy sector in 2021 worldwide, discussing some of the most relevant case studies and the meteorological conditions that led to them. We provide a perspective on their impacts on electricity generation, transmission and consumption, and summarize estimations of economic losses

Cannabis dampens the effects of music in brain regions sensitive to reward and emotion

Background: Despite the current shift towards permissive cannabis policies, few studies have investigated the pleasurable effects users seek. Here we investigate the effects of cannabis on listening to music - a rewarding activity that frequently occurs in the context of recreational cannabis use. We additionally tested how these effects are influenced by cannabidiol (CBD), which may offset cannabis-related harms. Methods: Across three sessions, sixteen cannabis users inhaled cannabis with CBD, cannabis without CBD, and placebo. We compared their response to music relative to control excerpts of scrambled sound during functional Magnetic Resonance Imaging (fMRI) within regions identified in a meta-analysis of music-evoked reward and emotion. All results were False Discovery Rate corrected (p<0.05). Results: Compared to placebo, cannabis without CBD dampened response to music in bilateral auditory cortex (right: p=0.005, left: p=0.008), right hippocampus/parahippocampal gyrus (p=0.025), right amygdala (p=0.025) and right ventral striatum (p=0.033). Across all sessions, the effects of music in this ventral striatal region correlated with pleasure ratings (p=0.002) and increased functional connectivity with auditory cortex (right: p=0.000, left: p=0.000), supporting its involvement in music reward. Functional connectivity between right ventral striatum and auditory cortex was increased by CBD (right: p=0.003, left: p=0.030), and cannabis with CBD did not differ from placebo on any fMRI measures. Both types of cannabis increased ratings of wanting to listen to music (p<0.002) and enhanced sound perception (p<0.001). Conclusions: Cannabis dampens the effects of music in brain regions sensitive to reward and emotion. These effects were offset by a key cannabis constituent, cannabidol

Weekly Intra-Amniotic IGF-1 Treatment Increases Growth of Growth-Restricted Ovine Fetuses and Up-Regulates Placental Amino Acid Transporters

Frequent treatment of the growth-restricted (IUGR) ovine fetus with intra-amniotic IGF-1 increases fetal growth. We aimed to determine whether increased growth was maintained with an extended dosing interval and to examine possible mechanisms. Pregnant ewes were allocated to three groups: Control, and two IUGR groups (induced by placental embolization) treated with weekly intra-amniotic injections of either saline (IUGR) or 360 µg IGF-1 (IGF1). IUGR fetuses were hypoxic, hyperuremic, hypoglycemic, and grew more slowly than controls. Placental glucose uptake and SLC2A1 (GLUT2) mRNA levels decreased in IUGR fetuses, but SLC2A3 (GLUT3) and SLC2A4 (GLUT4) levels were unaffected. IGF-1 treatment increased fetal growth rate, did not alter uterine blood flow or placental glucose uptake, and increased placental SLC2A1 and SLC2A4 (but not SLC2A3) mRNA levels compared with saline-treated IUGR animals. Following IGF-1 treatment, placental mRNA levels of isoforms of the system A, y+, and L amino acid transporters increased 1.3 to 5.0 fold, while the ratio of phosphorylated-mTOR to total mTOR also tended to increase. Weekly intra-amniotic IGF-1 treatment provides a promising avenue for intra-uterine treatment of IUGR babies, and may act via increased fetal substrate supply, up-regulating placental transporters for neutral, cationic, and branched-chain amino acids, possibly via increased activation of the mTOR pathway

Molecular and clinical predictors of improvement in progression-free survival with maintenance PARP inhibitor therapy in women with platinum-sensitive, recurrent ovarian cancer: A meta-analysis

BACKGROUND: The authors performed a meta‐analysis to better quantify the benefit of maintenance poly(ADP‐ribose) polymerase inhibitor (PARPi) therapy to inform practice in platinum‐sensitive, recurrent, high‐grade ovarian cancer for patient subsets with the following characteristics: germline BRCA mutation (gBRCAm), somatic BRCA mutation (sBRCAm), wild‐type BRCA but homologous recombinant‐deficient (HRD), homologous recombinant‐proficient (HRP), and baseline clinical prognostic characteristics. METHODS: Randomized trials comparing a PARPi versus placebo as maintenance treatment were identified from electronic databases. Treatment estimates of progression‐free survival were pooled across trials using the inverse variance weighted method. RESULTS: Four trials included 972 patients who received a PARPi (olaparib, 31%; niraparib, 35%; or rucaparib, 34%) and 530 patients who received placebo. For patients who had germline BRCA1 mutation (gBRCAm1) (N = 471), the hazard ratio (HR) was 0.29 (95% CI, 0.23‐0.37); for those who had germline BRCA2 mutation (gBRCAm2) (N = 236), the HR was 0.26 (95% CI, 0.17‐0.39); and, for those who had sBRCAm (N = 123), the HR was 0.22 (95% CI, 0.12‐0.41). The treatment effect was similar between the gBRCAm and sBRCAm subsets (P = .48). In patients who had wild‐type BRCA HRD tumors (excluding sBRCAm; N = 309), the HR was 0.41 (95% CI, 0.31‐0.56); and, in those who had wild‐type BRCA HRP tumors (N = 346), the HR was 0.64 (95% CI, 0.49‐0.83). The relative treatment effect was greater for the BRCAm versus HRD (P = .03), BRCAm versus HRP (P < .00001), and HRD versus HRP (P < .00001) subsets. There was no difference in benefit based on age, response after recent chemotherapy, and prior bevacizumab. CONCLUSIONS: In platinum‐sensitive, recurrent, high‐grade ovarian cancer, maintenance PARPi improves progression‐free survival for all patient subsets. PARPi therapy has a similar magnitude of benefit for sBRCAm and gBRCAm. Although patients with BRCAm derive the greatest benefit, the absence of a BRCAm or HRD could not be used to exclude patients from maintenance PARPi therapy

Detection of chromosome aberrations in metaphase and interphase tumor cells by in situ hybridization using chromosome-specific library probes

Chromosome aberrations in two glioma cell lines were analyzed using biotinylated DNA library probes that specifically decorate chromosomes 1, 4, 7, 18 and 22 from pter to qter. Numerical changes, deletions and rearrangements of these chromosomes were radily visualized in metaphase spreads, as well as in early prophase and interphase nuclei. Complete chromosomes, deleted chromosomes and segments of translocated chromosomes were rapidly delineated in very complex karyotypes. Simultaneous hybridizations with additional subregional probes were used to further define aberrant chromosomes. Digital image analysis was used to quantitate the total complement of specific chromosomal DNAs in individual metaphase and interphase cells of each cell line. In spite of the fact that both glioma lines have been passaged in vitro for many years, an under-representation of chromosome 22 and an over-representation of chromosome 7 (specifically 7p) were observed. These observations agree with previous studies on gliomas. In addition, sequences of chromosome 4 were also found to be under-represented, especially in TC 593. These analyses indicate the power of these methods for pinpointing chromosome segments that are altered in specific types of tumors

Loss of Function in Escherichia coli exposed to Environmentally Relevant Concentrations of Benzalkonium Chloride

Assessing the risk of resistance associated with biocide exposure commonly involves exposing microorganisms to biocides at concentrations close to the MIC. With the aim of representing exposure to environmental biocide residues, MG1655 was grown for 20 passages in the presence or absence of benzalkonium chloride (BAC) at 100 ng/L and 1000 ng/L (0.0002% and 0.002% of the MIC respectively). BAC susceptibility, planktonic growth rates, motility and biofilm-formation were assessed, and differentially expressed genes determined via RNA-sequencing. Planktonic growth rate and biofilm-formation were significantly reduced (p<0.001) following BAC adaptation, whilst BAC minimum bactericidal concentration increased two-fold. Transcriptomic analysis identified 289 upregulated and 391 downregulated genes after long-term BAC adaptation when compared to the respective control organism passaged in BAC-free-media. When the BAC-adapted bacterium was grown in biocide-free medium, 1052 genes were upregulated and 753 were down regulated. Repeated passage solely in biocide-free medium resulted in 460 upregulated and 476 downregulated genes compared to unexposed bacteria. Long-term exposure to environmentally relevant BAC concentrations increased the expression of genes associated with efflux and reduced gene expression associated with outer-membrane porins, motility and chemotaxis. This was manifested phenotypically through loss-of-function (motility). Repeated passage in a BAC-free-environment resulted in the up-regulation of multiple respiration-associated genes, which was reflected by increased growth rate. In summary, repeated exposure of to BAC residues resulted in significant alterations in global gene expression that were associated with minor decreases in biocide susceptibility, reductions in growth-rate and biofilm-formation, and loss of motility. Exposure to very low concentrations of biocide in the environment is a poorly understood risk factor for antimicrobial resistance. Repeated exposure to trace levels of the biocide BAC resulted in loss of function (motility) and a general reduction in bacterial fitness, but relatively minor decreases in susceptibility. These changes were accompanied by widespread changes in the transcriptome. This demonstrates the importance of including phenotypic characterisation in studies designed to assess the risks of biocide exposure. [Abstract copyright: Copyright © 2018 American Society for Microbiology.

Loss of Dictyostelium HSPC300 causes a scar-like phenotype and loss of SCAR protein

<p>Abstract</p> <p>Background</p> <p>SCAR/WAVE proteins couple signalling to actin polymerization, and are thus fundamental to the formation of pseudopods and lamellipods. They are controlled as part of a five-membered complex that includes the tiny HSPC300 protein. It is not known why SCAR/WAVE is found in such a large assembly, but in <it>Dictyostelium </it>the four larger subunits have different, clearly delineated functions.</p> <p>Results</p> <p>We have generated <it>Dictyostelium </it>mutants in which the HSPC300 gene is disrupted. As has been seen in other regulatory complex mutants, SCAR is lost in these cells, apparently by a post-translational mechanism, though PIR121 levels do not change. HSPC300 knockouts resemble <it>scar </it>mutants in slow migration, roundness, and lack of large pseudopods. However <it>hspc300</it>-colonies on bacteria are larger and more similar to wild type, suggesting that some SCAR function can survive without HSPC300. We find no evidence for functions of HSPC300 outside the SCAR complex.</p> <p>Conclusion</p> <p>HSPC300 is essential for most SCAR complex functions. The phenotype of HSPC300 knockouts is most similar to mutants in <it>scar</it>, not the other members of the SCAR complex, suggesting that HSPC300 acts most directly on SCAR itself.</p

Effects of Aesthetic Chills on a Cardiac Signature of Emotionality

Previous studies have shown that a cardiac signature of emotionality (referred to as EK, which can be computed from the standard 12 lead electrocardiogram, ECG), predicts inter-individual differences in the tendency to experience and express positive emotion. Here, we investigated whether EK values can be transiently modulated during stimulation with participant-selected music pieces and film scenes that elicit strongly positive emotion. The phenomenon of aesthetic chills, as indicated by measurable piloerection on the forearm, was used to accurately locate moments of peak emotional responses during stimulation. From 58 healthy participants, continuous EK values, heart rate, and respiratory frequency were recorded during stimulation with film scenes and music pieces, and were related to the aesthetic chills. EK values, as well as heart rate, increased significantly during moments of peak positive emotion accompanied by piloerection. These results are the first to provide evidence for an influence of momentary psychological state on a cardiac signature of emotional personality (as reflected in EK values). The possibility to modulate ECG amplitude signatures via stimulation with emotionally significant music pieces and film scenes opens up new perspectives for the use of emotional peak experiences in the therapy of disorders characterized by flattened emotionality, such as depression or schizoid personality disorder