Is gene activity in plant cells affected by UMTS-irradiation? A whole genome approach

Mobile phone technology makes use of radio frequency (RF) electromagnetic fields transmitted through a dense network of base stations in Europe. Possible harmful effects of RF fields on humans and animals are discussed, but their effect on plants has received little attention. In search for physiological processes of plant cells sensitive to RF fields, cell suspension cultures of Arabidopsis thaliana were exposed for 24 h to a RF field protocol representing typical microwave exposition in an urban environment. mRNA of exposed cultures and controls was used to hybridize Affymetrix-ATH1 whole genome microarrays. Differential expression analysis revealed significant changes in transcription of 10 genes, but they did not exceed a fold change of 2.5. Besides that 3 of them are dark-inducible, their functions do not point to any known responses of plants to environmental stimuli. The changes in transcription of these genes were compared with published microarray datasets and revealed a weak similarity of the microwave to light treatment experiments. Considering the large changes described in published experiments, it is questionable if the small alterations caused by a 24 h continuous microwave exposure would have any impact on the growth and reproduction of whole plants

Limited sensitivity and specificity of the ACR/EULAR-2019 classification criteria for SLE in JSLE?—observations from the UK JSLE Cohort Study

Objectives: This study aimed to test the performance of the new ACR and EULAR criteria, that include ANA positivity as entry criterion, in JSLE. / Methods: Performance of the ACR/EULAR-2019 criteria were compared with Systemic Lupus International Collaborating Clinics (SLICC-2012), using data from children and young people (CYP) in the UK JSLE Cohort Study (n = 482), with the ACR-1997 criteria used as reference standard. An unselected cohort of CYP positive for ANA (n = 129) was used to calculate positive/negative predictive values of the criteria. / Results: At both first and last visits, the number of patients fulfilling the different classification criteria varied significantly (P < 0.001). The sensitivity of the SLICC-2012 criteria was higher when compared with that of the ACR/EULAR-2019 criteria at first and last visits (98% vs 94% for first visit, and 98% vs 96% for last visit; P < 0.001), when all available CYP were considered. The ACR/EULAR-2019 criteria were more specific when compared with the SLICC-2012 criteria (77% vs 67% for first visit, and 81% vs 71% for last visit; P < 0.001). Significant differences between the classification criteria were mainly caused by the variation in ANA positivity across ages. In the unselected cohort of ANA-positive CYP, the ACR/EULAR-2019 criteria produced the highest false-positive classification (6/129, 5%). / Conclusion: In CYP, the ACR/EULAR-2019 criteria are not superior to those of the SLICC-2012 or ACR-1997 criteria. If classification criteria are designed to include CYP and adult populations, paediatric rheumatologists should be included in the consensus and evaluation process, as seemingly minor changes can significantly affect outcomes

Panel sequencing links rare, likely damaging gene variants with distinct clinical phenotypes and outcomes in juvenile-onset SLE

OBJECTIVES: Juvenile-onset systemic lupus erythematosus (jSLE) affects 15–20% of lupus patients. Clinical heterogeneity between racial groups, age groups and individual patients suggests variable pathophysiology. This study aimed to identify highly penetrant damaging mutations in genes associated with SLE/SLE-like disease in a large national cohort (UK JSLE Cohort Study) and compare demographic, clinical and laboratory features in patient sub-cohorts with ‘genetic’ SLE vs remaining SLE patients. METHODS: Based on a sequencing panel designed in 2018, target enrichment and next-generation sequencing were performed in 348 patients to identify damaging gene variants. Findings were integrated with demographic, clinical and treatment related datasets. RESULTS: Damaging gene variants were identified in ∼3.5% of jSLE patients. When compared with the remaining cohort, ‘genetic’ SLE affected younger children and more Black African/Caribbean patients. ‘Genetic’ SLE patients exhibited less organ involvement and damage, and neuropsychiatric involvement developed over time. Less aggressive first line treatment was chosen in ‘genetic’ SLE patients, but more second and third line agents were used. ‘Genetic’ SLE associated with anti-dsDNA antibody positivity at diagnosis and reduced ANA, anti-LA and anti-Sm antibody positivity at last visit. CONCLUSION: Approximately 3.5% of jSLE patients present damaging gene variants associated with younger age at onset, and distinct clinical features. As less commonly observed after treatment induction, in ‘genetic’ SLE, autoantibody positivity may be the result of tissue damage and explain reduced immune complex-mediated renal and haematological involvement. Routine sequencing could allow for patient stratification, risk assessment and target-directed treatment, thereby increasing efficacy and reducing toxicity

Therapeutic concentrations of glucagon-like peptide-1 in cerebrospinal fluid following cell-based delivery into the cerebral ventricles of cats

<p>Abstract</p> <p>Background</p> <p>Neuropeptides may have considerable potential in the treatment of acute and chronic neurological diseases. Encapsulated genetically engineered cells have been suggested as a means for sustained local delivery of such peptides to the brain. In our experiments, we studied human mesenchymal stem cells which were transfected to produce glucagon-like peptide-1 (GLP-1).</p> <p>Methods</p> <p>Cells were packed in a water-permeable mesh bag containing 400 polymeric microcapsules, each containing 3000 cells. The mesh bags were either transplanted into the subdural space, into the brain parenchyma or into the cerebral ventricles of the cat brain. Mesh bags were explanted after two weeks, and cell viability, as well as GLP-1 concentration in the cerebrospinal fluid (CSF), was measured.</p> <p>Results</p> <p>Viability of cells did not significantly differ between the three implantation sites. However, CSF concentration of GLP-1 was significantly elevated only after ventricular transplantation with a maximum concentration of 73 pM (binding constant = 70 pM).</p> <p>Conclusions</p> <p>This study showed that ventricular cell-based delivery of soluble factors has the capability to achieve concentrations in the CSF which may become pharmacologically active. Despite the controversy about the pharmacokinetic limitations of ventricular drug delivery, there might be a niche in this for encapsulated cell biodelivery of soluble, highly biologically-effective neuropeptides of low molecular weight like GLP-1.</p

Coprophagous features in carnivorous Nepenthes plants: a task for ureases

Most terrestrial carnivorous plants are specialized on insect prey digestion to obtain additional nutrients. Few species of the genus Nepenthes developed mutualistic relationships with mammals for nitrogen supplementation. Whether dietary changes require certain enzymatic composition to utilize new sources of nutrients has rarely been tested. Here, we investigated the role of urease for Nepenthes hemsleyana that gains nitrogen from the bat Kerivoula hardwickii while it roosts inside the pitchers. We hypothesized that N. hemsleyana is able to use urea from the bats’ excrements. In fact, we demonstrate that 15N-enriched urea provided to Nepenthes pitchers is metabolized and its nitrogen is distributed within the plant. As ureases are necessary to degrade urea, these hydrolytic enzymes should be involved. We proved the presence and enzymatic activity of a urease for Nepenthes plant tissues. The corresponding urease cDNA from N. hemsleyana was isolated and functionally expressed. A comprehensive phylogenetic analysis for eukaryotic ureases, including Nepenthes and five other carnivorous plants’ taxa, identified them as canonical ureases and reflects the plant phylogeny. Hence, this study reveals ureases as an emblematic example for an efficient, low-cost but high adaptive plasticity in plants while developing a further specialized lifestyle from carnivory to coprophagy

Is the Multiverse Hypothesis capable of explaining the Fine Tuning of Nature Laws and Constants? The Case of Cellular Automata

The objective of this paper is analyzing to which extent the multiverse hypothesis provides a real explanation of the peculiarities of the laws and constants in our universe. First we argue in favor of the thesis that all multiverses except Tegmark's > are too small to explain the fine tuning, so that they merely shift the problem up one level. But the > is surely too large. To prove this assessment, we have performed a number of experiments with cellular automata of complex behavior, which can be considered as universes in the mathematical multiverse. The analogy between what happens in some automata (in particular Conway's >) and the real world is very strong. But if the results of our experiments can be extrapolated to our universe, we should expect to inhabit -- in the context of the multiverse -- a world in which at least some of the laws and constants of nature should show a certain time dependence. Actually, the probability of our existence in a world such as ours would be mathematically equal to zero. In consequence, the results presented in this paper can be considered as an inkling that the hypothesis of the multiverse, whatever its type, does not offer an adequate explanation for the peculiarities of the physical laws in our world. A slightly reduced version of this paper has been published in the Journal for General Philosophy of Science, Springer, March 2013, DOI: 10.1007/s10838-013-9215-7.Comment: 30 pages, 16 figures, 5 tables. Slightly reduced version published in Journal for General Philosophy of Scienc

Neuropsychiatric involvement in juvenile-onset systemic lupus erythematosus: Data from the UK Juvenile-onset systemic lupus erythematosus cohort study

INTRODUCTION: Juvenile-onset systemic lupus erythematosus (JSLE) is a rare autoimmune/inflammatory disease with significant morbidity and mortality. Neuropsychiatric (NP) involvement is a severe complication, encompassing a heterogeneous range of neurological and psychiatric manifestations. METHODS: Demographic, clinical, and laboratory features of NP-SLE were assessed in participants of the UK JSLE Cohort Study, and compared to patients in the same cohort without NP manifestations. RESULTS: A total of 428 JSLE patients were included in this study, 25% of which exhibited NP features, half of them at first visit. Most common neurological symptoms among NP-JSLE patients included headaches (78.5%), mood disorders (48.6%), cognitive impairment (42%), anxiety (23.3%), seizures (19.6%), movement disorders (17.7%), and cerebrovascular disease (14.9%). Peripheral nervous system involvement was recorded in 7% of NP-SLE patients. NP-JSLE patients more frequently exhibited thrombocytopenia (<100 × 109/L) (p = 0.04), higher C-reactive protein levels (p = 0.01), higher global pBILAG score at first visit (p < 0.001), and higher SLICC damage index score at first (p = 0.02) and last (p < 0.001) visit when compared to JSLE patients without NP involvement. CONCLUSIONS: A significant proportion of JSLE patients experience NP involvement (25%). Juvenile-onset NP-SLE most commonly affects the CNS and is associated with increased overall disease activity and damage

COVID-19: treatment strategies of German-speaking pediatric rheumatologists Results of an online survey

Zusammenfassung Hintergrund Zuverlässige Daten zu Verlauf und Therapie von COVID-19 („corona virus disease 2019“) bei Kindern mit rheumatischen Erkrankungen unter Immunsuppression fehlen. Ziel der Arbeit Abbildung individueller Strategien der Mitglieder der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR) im Umgang mit COVID-19. Methodik Mittels Online-Umfrage wurden im Mai 2020 das Meinungsbild der GKJR-Mitglieder zum Umgang mit DMARDs („disease-modifying anti-rheumatic drugs“) bei COVID-19-Erkrankung sowie die Bereitschaft zum Einsatz spezieller Therapieansätze bei Patienten mit unterschiedlicher Schwere von COVID-19 erhoben. Ergebnisse Es nahmen 71 Kollegen (27,3 % aller befragten ärztlichen Mitglieder) an der Umfrage teil; davon hatten 28,2 % bereits Patienten mit COVID-19 betreut. Über 95 % der Teilnehmer lehnten eine präventive Anpassung der antirheumatischen Therapie im Rahmen der SARS-CoV-2-Pandemie ab. Bei ambulanten Patienten unter Immunsuppression mit nachgewiesener COVID-19-Erkrankung würden mehr als 50 % der Teilnehmer folgende Therapien aussetzen: intravenöse hoch dosierte Steroide, Cyclophosphamid, Anti-CD20-Antikörper, sowie eine BAFF-, CTLA-4-, TNF-α-Blockade. Hingegen würden nichtsteroidale Antiphlogistika, Hydroxychloroquin (HCQ), orale Steroide, Mycophenolat, IL-1-Blockade sowie Immunglobuline (Ig) von &amp;gt;70 % der Kollegen weiter fortgeführt. Bei stationären Patienten mit COVID-19 würden insgesamt 74,6 % der Kollegen eine COVID-19-gerichtete Therapie erwägen. Bei stabilem Verlauf unter O 2 -Therapie (Stufe I) würden am häufigsten HCQ (18,3 %), Azithromycin (16,9 %) und Ig (9,9 %) in Betracht gezogen. Bei drohendem (Stufe II) bzw. manifestem Zytokinsturm (Stufe III) würden am häufigsten Anakinra (40,8 % bei Stufe II bzw. 46,5 % bei Stufe III), Tocilizumab (26,8 % bzw. 40,8 %), Steroide (25,4 % bzw. 33,8 %) und Remdesivir (29,6 % bzw. 38,0 %) eingesetzt. Von vielen Kollegen wurde betont, dass die Therapiestrategie individuell und der klinischen Situation entsprechend angepasst werden soll. Diskussion Die Ergebnisse der Online-Umfrage sind vor dem Hintergrund einer aktuell in Deutschland niedrigen Prävalenz von COVID-19 zu sehen und spiegeln somit theoretische Überlegungen der Befragten wider. Da Kinder derzeit nicht im Fokus von prospektiven COVID-19-Studien stehen, scheint der kontinuierliche und kritische kollegiale Fachaustausch bei Therapieentscheidungen umso wichtiger zu sein