A novel function for the Mre11-Rad50-Xrs2 complex in base excision repair

The Mre11/Rad50/Xrs2 (MRX) complex in Saccharomyces cerevisiae has well-characterized functions in DNA double-strand break processing, checkpoint activation, telomere length maintenance and meiosis. In this study, we demonstrate an involvement of the complex in the base excision repair (BER) pathway. We studied the repair of methyl-methanesulfonate-induced heat-labile sites in chromosomal DNA in vivo and the in vitro BER capacity for the repair of uracil- and 8-oxoG-containing oligonucleotides in MRX-deficient cells. Both approaches show a clear BER deficiency for the xrs2 mutant as compared to wildtype cells. The in vitro analyses revealed that both subpathways, long-patch and short-patch BER, are affected and that all components of the MRX complex are similarly important for the new function in BER. The investigation of the epistatic relationship of XRS2 to other BER genes suggests a role of the MRX complex downstream of the AP-lyases Ntg1 and Ntg2. Analysis of individual steps in BER showed that base recognition and strand incision are not affected by the MRX complex. Reduced gap-filling activity and the missing effect of aphidicoline treatment, an inhibitor for polymerases, on the BER efficiency indicate an involvement of the MRX complex in providing efficient polymerase activity

Laser-induced acceleration of Helium ions from unpolarized gas jets

In order to develop a laser-driven spin-polarized ³He-ion beam source available for nuclear-physics experiments as well as for the investigation of polarized nuclear fusion, several challenges have to be overcome. Apart from the provision of a properly polarized ³He gas-jet target, one of the biggest milestones is the demonstration of the general feasibility of laser-induced ion acceleration out of gas-jet targets. Of particular importance is the knowledge about the main ion-emission angles as well as the achievable ion-energy spectra (dependent on the optimal set of laser and target parameters). We report on the results of such a feasibility study performed at PHELIX, GSI Darmstadt. Both ³He- and ⁴He-gas jets (ngas ∼ 10¹⁹ cm⁻³) were illuminated with high-intensity laser pulses, IL ∼ O (10¹⁹ W cm⁻²). The main ion-emission angles could be identified (±90° with respect to the laser-propagation direction) and the ion-energy spectra for all ion species could be extracted: for the optimal laser and target parameters, the high-energy cut-offs for He ²⁺,¹⁺ ions were 4.65 MeV (with a normalized energy uncertainty of Δ ɛ​ ɛ​⁻¹ = 0.033) and 3.27 MeV (Δ ɛ​ ɛ​⁻¹= 0.055), respectively

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

Purpose: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. Methods: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. Results: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. Conclusions: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19

raw_data

The data file consists of the data for egg survival, hatchling survival, head capsule width, pupation/eclosion rate and adult heat survival with body mass

Data from: Carried over: heat stress in the egg stage reduces subsequent performance in a butterfly

Increasing heat stress caused by anthropogenic climate change may pose a substantial challenge to biodiversity due to associated detrimental effects on survival and reproduction. Therefore, heat tolerance has recently received substantial attention, but its variation throughout ontogeny and effects carried over from one developmental stage to another remained largely neglected. To explore to what extent stress experienced early in life affects later life stages, we here investigate effects of heat stress experienced in the egg stage throughout ontogeny in the tropical butterfly Bicyclus anynana. We found that detrimental effects of heat stress in the egg stage were detectable in hatchlings, larvae and even resulting adults, as evidenced by decreased survival, growth, and body mass. This study shows that even in holometabalous insects with discrete life stages effects of stress experienced early in life are carried over to later stages, substantially reducing subsequent fitness. We argue that such effects need to be considered when trying to forecast species responses to climate change

Results of general linear mixed models (GLMMs) for the effects of egg temperature (fixed), cage (nested within temperature; random), and sex (fixed) on (a) adult body mass, (b) thorax-abdomen ratio, and (c) abdomen fat content in <i>Bicyclus anynana</i>.

<p>Significant <i>P</i>-values are given in bold.</p

Schematic figure of the experimental design used.

<p>Eggs collected from stock population females were randomly divided and exposed to six temperatures for 24 hours each. Thereafter, one day-old hatchlings were exposed to either 27°C or 37°C, after which survival and head capsule width were measured. Another cohort of resulting hatchlings was reared under control conditions until adult eclosion and then exposed for 24 h to 37°C, after which heat survival and other traits were scored.</p

Results of general linear models (GLMs) for the effects of (a) egg temperature on egg survival rate, (b) egg temperature and larval heat stress on hatchling survival rate, (c) egg temperature, larval heat stress and survival (dead versus alive individuals) on head capsule width of hatchlings, and for the effects of egg temperature on the survival rate during (d) the larval and (e) the pupal stage in <i>Bicyclus anynana</i>.

<p>Significant <i>P</i>-values are given in bold.</p

Results of a nominal logistic regression for the effects of egg temperature (fixed), cage (nested within temperature; random), sex (fixed), adult body mass, thorax-abdomen ratio and abdomen fat content (covariates) on adult heat survival in <i>Bicyclus anynana</i>.

<p>Significant <i>P</i>-values are given in bold.</p