Atmospheric conditions favouring extreme precipitation and flash floods in temperate regions of Europe

In recent years, flash floods have repeatedly occurred in temperate regions of central western Europe. Unlike in Mediterranean catchments, this flooding behaviour is unusual. In the past (especially in the 1990s), floods have been characterized by predictable, slowly rising water levels during winter and driven by westerly atmospheric fluxes. Here, we explore potential links and causes between the recent occurrence of flash floods in central western Europe to extreme precipitation and specific atmospheric conditions. We hypothesize that a change in atmospheric conditions has led to more frequent extreme precipitation events that have subsequently triggered flash flood events in central western Europe. To test this hypothesis, we compiled data on flash floods in central western Europe and selected precipitation events above 40 mm h$^{−1}$ from radar data (the RADOLAN “Radar-Online-Adjustment” dataset from the German Weather Service). Moreover, we identified proxy parameters representative of extreme precipitation favouring atmospheric conditions from the ERA5 reanalysis dataset. High specific humidity (q) in the lower troposphere (q≥0.004 kg kg$^{−1}$), sufficient latent instability (convective available potential energy (CAPE) ≥ 327 J kg$^{−1}$), and weak wind speeds between 10 m a.g.l. and 500 hPa (WS$_{10 m−500 hPa}$ ≤ 6 m s$^{−1}$) proved to be characteristic of intense rainfall that can potentially trigger flash floods. We relied on linear models to analyse 40 years worth (1981–2020) of atmospheric parameters as well as related precipitation events. We found significant increases in the atmospheric moisture content and increases in atmospheric instability. Parameters representing the motion and organization of convective systems remained largely unchanged in the considered period (1981–2020); however, the number of precipitation events, their maximum 5 min intensities, and their hourly sums were characterized by large interannual variations, and no trends could be identified between 2002 and 2020. Our study shows that there is no single mechanistic path leading from atmospheric conditions to extreme precipitation and subsequently to flash floods. The interactions between the processes involved are so intricate that more analyses which consider other potentially relevant factors, such as intra-annual precipitation patterns or catchment-specific parameters, are required

Functional Outcomes of Brolucizumab-Induced Intraocular Inflammation Involving the Posterior Segment-A Meta-Analysis and Systematic Review.

Early poor outcomes of intraocular inflammation (IOI) after intravitreal brolucizumab (IVB) have negatively affected the use of brolucizumab in clinical routine. We wished to identify factors related to the treatment details of IOI involving the posterior segment resulting from IVB for neovascular AMD (nAMD), if these were reported in detail. Articles were retrieved from PubMed, Scopus, ClinicalTrials, and CENTRAL using the following search terms: AND AND . The risk of bias was rated using the JBI Critical Appraisal Tool. We included 31 reports (41 patients and 46 eyes). Patients were 75.9 ± 8.5 years, and 58.5% were female. IOI occurred 41.7 ± 37.5 (median 37.0) days after treatment initiation with 2.0 ± 1.3 (1-6) IVB injections. A mean change in visual acuity of -14.6 ± 21.0 (median -6.5) letters was reported. The mean time from first IOI signs to the initiation of any anti-inflammatory treatment was 3.3 ± 6.2 days, with 63% of the patients receiving systemic corticosteroids as standard treatment. Finally, a period effect was observed, with a change in visual acuity of -25.3 ± 27.1 and -2.6 ± 7.3 letters in the chronologically first and last third, respectively, of treated eyes (effect size: r = 0.71; p = 0.006). Functional outcomes markedly improved with increasing experience in managing IOI

The dose makes the poison: feeding of antibiotic-treated winter honey bees, Apis mellifera, with probiotics and b-vitamins

Honey stores of Apis mellifera colonies are replaced with sugar water by beekeepers, which may result in malnutrition. Nutritional supplements have been developed, but the importance of bacterial probiotics and vitamins is poorly understood. Given that supplementary feeding with vitamins and probiotics may enhance worker weight and longevity, this might suggest a feasible approach to mitigate winter colony losses. Here, we conducted a laboratory hoarding cage study with freshly emerged winter bees, which were treated with the antibiotic tetracycline to reduce gut bacteria obtained post-emergence and subsequently assigned to feeding regimes: sucrose only, sucrose + pollen, probiotics (low and high dosage), probiotics + pollen (low and high dosage), or b-vitamins (low and high dosage), (N=8 treatments, 29 workers/cage x8 replicates). In parallel, another age cohort of bees remained on their frame (=Frame) to establish their gut microbiota and were subsequently fed with sucrose only or sucrose + pollen (N=2 treatments, 29 workers/cage x4 replicates). The most beneficial effects on body weights were found in workers given ad libitum access to pollen, notably in the Frame Sucrose + Pollen group, confirming the inherent importance of post-emergent gut flora inoculation and the role of gut bacteria in protein digestion. Furthermore, both Frame groups and the antibiotic-treated workers fed with probiotic low + pollen survived longer than all other groups, highlighting an fundamental host-microbial relationship. On the other hand, our current treatments alone, post-tetracycline, did not yield any positive results. In contrast, high dosages of both probiotic and b-vitamins significantly reduced life span compared to their low concentration counterparts, probably due to dysbiosis and toxicity, suggesting that the outcome was dose-dependent. These results highlight that bacterial supplementation can alter longevity with advisable caution since harmful concentrations appear to exist

Dream team for honey bee health: pollen and unmanipulated gut microbiota promote worker longevity and body weight

Gut microbiota are known to foster pollen digestion in honey bee workers, Apis mellifera, thereby enhancing longevity and body weight gain. However, it is currently not known how longevity and body weight gain are effected when gut microbiota are reduced in bees with or without access to pollen. Here, using a hoarding cage set-up with freshly emerged summer workers, we manipulated the gut microbiota of half the bees with the antibiotic tetracycline (ABX), and left the other half untreated on a sucrose solution diet. Afterwards, all bees were assigned to either sucrose diets or sucrose plus ad libitum access to pollen (N=4 treatments, N=26 bees/treatment, N=10 replicates/treatment, N=1040 total workers). The data confirm that pollen has a positive effect on longevity and body weight in workers with an unmanipulated gut microbiota. Surprisingly, the antibiotics alone also improved the longevity and body weight of the workers fed a strictly sucrose diet, potentially explained by the reduction of harmful bacteria. However, this positive effect was reversed from an observed antagonistic interaction between pollen and antibiotics, underscoring the innate value of natural microbiota on pollen digestion. In conclusion, a combination of adequate pollen supply and an unmanipulated gut microbiota appears crucial to honey bee worker health, calling for respective efforts to ensure both in managed colonies

The Impact of Sarcopenia in the Long-Term Survival of Patients following Complex Endovascular Aortic Surgery for Thoracoabdominal Aortic Aneurysms

Objectives: Image-based sarcopenia has been the subject of recent studies, hypothesized as a prognostic factor for patients with thoracoabdominal aortic aneurysms. Methods and Materials: We conducted a single-center retrospective analysis of patients who underwent complex endovascular repair for thoracoabdominal aortic aneurysms between 2008 and 2016. CT image assessment was performed and patients were classified as sarcopenic and non-sarcopenic using two stratification methods: skeletal mass index (SMI) and total psoas muscle index (TPMI). According to sex, each patient was defined as sarcopenic if their SMI or TPMI was in the lowest third of the study group. The primary endpoint was impact of sarcopenia on perioperative mortality and long-term survival. Secondary endpoints were perioperative complications. Results: From a total of 155 patients, 135 were eligible for study. Overall, in-hospital mortality was 5.9% (8/135). The 30-day, 1-year, 3-year and 5-year mortality was 10.4% (14/135), 20% (27/135), 28.1% (38/135) and 31.1% (42/135), respectively. There was no difference in the long-term mortality rates between sarcopenic and non-sarcopenic patients regardless of the stratification method used (p = 0.4 for SMI and p = 0.2 for TPMI). According to SMI, 30-day mortality of sarcopenic patients was significantly lower in comparison to non-sarcopenic patients (1/45, 2.2% vs. 13/90, 14.4%, p = 0.028). Based on the total psoas muscle index, sarcopenic patients were at higher risk for development of pulmonary complications in comparison to non-sarcopenic patients postoperatively (p = 0.03). Conclusion: Using SMI and TPMI, sarcopenia was not associated with reduced long-term survival in patients undergoing complex endovascular repair for thoracoabdominal aortic aneurysms

Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization

Genotype–phenotype associations within the Li-Fraumeni spectrum: a report from the German Registry

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by pathogenic TP53 variants. The condition represents one of the most relevant genetic causes of cancer in children and adults due to its frequency and high cancer risk. The term Li-Fraumeni spectrum reflects the evolving phenotypic variability of the condition. Within this spectrum, patients who meet specific LFS criteria are diagnosed with LFS, while patients who do not meet these criteria are diagnosed with attenuated LFS. To explore genotype–phenotype correlations we analyzed 141 individuals from 94 families with pathogenic TP53 variants registered in the German Cancer Predisposition Syndrome Registry. Twenty-one (22%) families had attenuated LFS and 73 (78%) families met the criteria of LFS. NULL variants occurred in 32 (44%) families with LFS and in two (9.5%) families with attenuated LFS (P value < 0.01). Kato partially functional variants were present in 10 out of 53 (19%) families without childhood cancer except adrenocortical carcinoma (ACC) versus 0 out of 41 families with childhood cancer other than ACC alone (P value < 0.01). Our study suggests genotype–phenotype correlations encouraging further analyses. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13045-022-01332-1

Monoallelic Expression of Multiple Genes in the CNS

The inheritance pattern of a number of major genetic disorders suggests the possible involvement of genes that are expressed from one allele and silent on the other, but such genes are difficult to detect. Since DNA methylation in regulatory regions is often a mark of gene silencing, we modified existing microarray-based assays to detect both methylated and unmethylated DNA sequences in the same sample, a variation we term the MAUD assay. We probed a 65 Mb region of mouse Chr 7 for gene-associated sequences that show two distinct DNA methylation patterns in the mouse CNS. Selected genes were then tested for allele-specific expression in clonal neural stem cell lines derived from reciprocal F1 (C57BL/6×JF1) hybrid mice. In addition, using a separate approach, we directly analyzed allele-specific expression of a group of genes interspersed within clusters of OlfR genes, since the latter are subject to allelic exclusion. Altogether, of the 500 known genes in the chromosomal region surveyed, five show monoallelic expression, four identified by the MAUD assay (Agc1, p (pink-eyed dilution), P4ha3 and Thrsp), and one by its proximity to OlfR genes (Trim12). Thrsp (thyroid hormone responsive SPOT14 homolog) is expressed in hippocampus, but the human protein homolog, S14, has also been implicated in aggressive breast cancer. Monoallelic expression of the five genes is not coordinated at a chromosome-wide level, but rather regulated at individual loci. Taken together, our results suggest that at least 1% of previously untested genes are subject to allelic exclusion, and demonstrate a dual approach to expedite their identification

Genomic aberrations associated with outcome in anaplastic oligodendroglial tumors treated within the EORTC phase III trial 26951

Despite similar morphological aspects, anaplastic oligodendroglial tumors (AOTs) form a heterogeneous clinical subgroup of gliomas. The chromosome arms 1p/19q codeletion has been shown to be a relevant biomarker in AOTs and to be perfectly exclusive from EGFR amplification in gliomas. To identify new genomic regions associated with prognosis, 60 AOTs from the EORTC trial 26951 were analyzed retrospectively using BAC-array-based comparative genomic hybridization. The data were processed using a binary tree method. Thirty-three BACs with prognostic value were identified distinguishing four genomic subgroups of AOTs with different prognosis (p < 0.0001). Type I tumors (25%) were characterized by: (1) an EGFR amplification, (2) a poor prognosis, (3) a higher rate of necrosis, and (4) an older age of patients. Type II tumors (21.7%) had: (1) loss of prognostic BACs located on 1p tightly associated with 19q deletion, (2) a longer survival, (3) an oligodendroglioma phenotype, and (4) a frontal location in brain. Type III AOTs (11.7%) exhibited: (1) a deletion of prognostic BACs located on 21q, and (2) a short survival. Finally, type IV tumors (41.7%) had different genomic patterns and prognosis than type I, II and III AOTs. Multivariate analysis showed that genomic type provides additional prognostic data to clinical, imaging and pathological features. Similar results were obtained in the cohort of 45 centrally reviewed–validated cases of AOTs. Whole genome analysis appears useful to screen the numerous genomic abnormalities observed in AOTs and to propose new biomarkers particularly in the non-1p/19q codeleted AOTs

Targeting Several CAG Expansion Diseases by a Single Antisense Oligonucleotide

To date there are 9 known diseases caused by an expanded polyglutamine repeat, with the most prevalent being Huntington's disease. Huntington's disease is a progressive autosomal dominant neurodegenerative disorder for which currently no therapy is available. It is caused by a CAG repeat expansion in the HTT gene, which results in an expansion of a glutamine stretch at the N-terminal end of the huntingtin protein. This polyglutamine expansion plays a central role in the disease and results in the accumulation of cytoplasmic and nuclear aggregates. Here, we make use of modified 2′-O-methyl phosphorothioate (CUG)n triplet-repeat antisense oligonucleotides to effectively reduce mutant huntingtin transcript and protein levels in patient-derived Huntington's disease fibroblasts and lymphoblasts. The most effective antisense oligonucleotide, (CUG)7, also reduced mutant ataxin-1 and ataxin-3 mRNA levels in spinocerebellar ataxia 1 and 3, respectively, and atrophin-1 in dentatorubral-pallidoluysian atrophy patient derived fibroblasts. This antisense oligonucleotide is not only a promising therapeutic tool to reduce mutant huntingtin levels in Huntington's disease but our results in spinocerebellar ataxia and dentatorubral-pallidoluysian atrophy cells suggest that this could also be applicable to other polyglutamine expansion disorders as well