Mediterranean winter rainfall in phase with African monsoons during the past 1.36 million years.

Mediterranean climates are characterized by strong seasonal contrasts between dry summers and wet winters. Changes in winter rainfall are critical for regional socioeconomic development, but are difficult to simulate accurately1 and reconstruct on Quaternary timescales. This is partly because regional hydroclimate records that cover multiple glacial-interglacial cycles2,3 with different orbital geometries, global ice volume and atmospheric greenhouse gas concentrations are scarce. Moreover, the underlying mechanisms of change and their persistence remain unexplored. Here we show that, over the past 1.36 million years, wet winters in the northcentral Mediterranean tend to occur with high contrasts in local, seasonal insolation and a vigorous African summer monsoon. Our proxy time series from Lake Ohrid on the Balkan Peninsula, together with a 784,000-year transient climate model hindcast, suggest that increased sea surface temperatures amplify local cyclone development and refuel North Atlantic low-pressure systems that enter the Mediterranean during phases of low continental ice volume and high concentrations of atmospheric greenhouse gases. A comparison with modern reanalysis data shows that current drivers of the amount of rainfall in the Mediterranean share some similarities to those that drive the reconstructed increases in precipitation. Our data cover multiple insolation maxima and are therefore an important benchmark for testing climate model performance.

1.36 million years of Mediterranean forest refugium dynamics in response to glacial-interglacial cycle strength.

The sediment record from Lake Ohrid (Southwestern Balkans) represents the longest continuous lake archive in Europe, extending back to 1.36 Ma. We reconstruct the vegetation history based on pollen analysis of the DEEP core to reveal changes in vegetation cover and forest diversity during glacial-interglacial (G-IG) cycles and early basin development. The earliest lake phase saw a significantly different composition rich in relict tree taxa and few herbs. Subsequent establishment of a permanent steppic herb association around 1.2 Ma implies a threshold response to changes in moisture availability and temperature and gradual adjustment of the basin morphology. A change in the character of G-IG cycles during the Early-Middle Pleistocene Transition is reflected in the record by reorganization of the vegetation from obliquity- to eccentricity-paced cycles. Based on a quantitative analysis of tree taxa richness, the first large-scale decline in tree diversity occurred around 0.94 Ma. Subsequent variations in tree richness were largely driven by the amplitude and duration of G-IG cycles. Significant tree richness declines occurred in periods with abundant dry herb associations, pointing to aridity affecting tree population survival. Assessment of long-term legacy effects between global climate and regional vegetation change reveals a significant influence of cool interglacial conditions on subsequent glacial vegetation composition and diversity. This effect is contrary to observations at high latitudes, where glacial intensity is known to control subsequent interglacial vegetation, and the evidence demonstrates that the Lake Ohrid catchment functioned as a refugium for both thermophilous and temperate tree species.

Sequential use of the Demoralization Scale in palliative care: feasibility, strain, and personal benefits of participation for patients at the end of life.

PURPOSE: To determine the efficacy of specifically targeted interventions in palliative care, sequential use of the Demoralization Scale (DS) could be a useful approach. This study's main objective was to evaluate the weekly use of the DS for palliative care inpatients. Secondary objectives were the analysis of the DS, self-perceived strain, and personal benefits of the assessment. METHODS: Patients admitted to 3 palliative care units (PCUs) were tested for eligibility and asked to complete the DS weekly. Self-perceived strain was rated on a numeric scale (0-10). Open questions about strain and helpfulness of the survey were asked. RESULTS: Over 10 months, 568 patients were admitted to the PCUs; 193 patients were eligible. A total of 120 patients participated once, of whom only 41 (34.1%) participated at least twice. The mean self-perceived strain caused by the assessment was 1.53 at T1 (N = 117, SD = 2.27, max = 8). CONCLUSIONS: While the single use of the DS in PCUs seems justified in view of the possibility to detect severe demoralization with overall low to moderate strain and self-perceived helpfulness for patients, the feasibility of the sequential use of the DS has to be regarded critically. Our study undermines the complexity of assessing changes in self-reported psychological phenomena with end-of-life patients at a PCU. The most limiting factors for participating twice were that patients were either discharged from hospital or declined further participation.

Effects of organic removal techniques prior to carbonate stable isotope analysis of lacustrine marls: A case study from palaeo-lake Fucino (central Italy).

RATIONALE: The suitability of organic matter (OM) removal pre-treatments in isotopic studies of lacustrine carbonates is currently under debate. Naturally occurring OM seems to have a negligible effect on the bulk isotopic composition of carbonates compared with changes induced by pre-treatments. This study provides further insights into the possible effects induced by commonly used pre-treatments on natural lacustrine carbonates. METHODS: Sixteen samples from the Fucino F1-F3 lacustrine succession (Abruzzo, central Italy) were characterised for their mineralogical and geochemical composition and each was split into three identical aliquots. One aliquot was left untreated while the remaining two were treated with NaOCl and H2 O2 dilutions. The same treatment was applied to an internal standard consisting of pure Carrara marble. The treated and untreated samples were analysed for their carbon (δ13 C values) and oxygen (δ18 O values) isotope compositions using an Analytical Precision AP2003 isotope ratio mass spectrometer. RESULTS: The samples had variable proportions of endogenic and detrital components, the detrital portion being more (less) abundant during colder (warmer) climate phases. We observed that neither the NaOCl nor the H2 O2 treatment was able to completely remove OM and therefore there was selective removal of compounds within the OM pool. A possible effect of pre-treatment is the loss of carbonates intimately interspersed within the OM, as suggested by the evolution of isotopic ratios towards the local detrital array. CONCLUSIONS: Our study highlights sample-specific changes in geochemistry associated with sample pre-treatments; however, such changes do not seem to lead to either systematic and/or predictable isotopic shifts. We suggest that the suitability of NaOCl or H2 O2 pre-treatments for OM removal should be evaluated on a case-by-case basis. In the specific case of lacustrine marls from palaeo-lake Fucino containing relatively low amounts of OM and in which both detrital and endogenic carbonates occur, both pre-treatments should be avoided.

Exploration of a Au(i)-mediated three-component reaction for the synthesis of DNA-tagged highly substituted spiroheterocycles.

We demonstrate a Au(i)-mediated three-component reaction to DNA-tagged highly substituted 6-oxa-1,2-diazaspiro[4.4]nonanes from either DNA-coupled aldehydes, hydrazides, or alkynols. The choice of the starting material coupled to the DNA tag was critial for the purity of the product as the DNA-aldehyde conjugate yielded the purest products, whereas the alkynol- and hydrazide conjugates returned complex product mixtures. The reaction was compatible with thymine-, cytosine-, and, surprisingly, with adenine-DNA, while guanine-containing DNA strands were degraded under the reaction conditions.

Gold-catalyzed three-component spirocyclization: a one-pot approach to functionalized pyrazolidines.

An efficient, highly atom economic synthesis of hitherto unknown spirocyclic pyrazolidines in a one-pot process was developed. The gold-catalyzed three-component coupling of alkynols, hydrazines and aldehydes or ketones likely proceeds via cycloisomerization of the alkynol to an exocyclic enol ether and subsequent [3 + 2]-cycloaddition of an azomethine ylide. A library of 29 derivatives with a wide range of functional groups was synthesized in up to 97% yield. With this new method, every position in the final product can be substituted which renders the method ideal for applications in combinatorial or medicinal chemistry.

"Scanxiety" and a sense of control: the perspective of lung cancer survivors and their caregivers on follow-up - a qualitative study.

OBJECTIVES: Lung cancer survivors often suffer from physical, emotional and social long-term effects of disease and treatment. Caregivers are also affected by the cancer diagnosis throughout the course of the disease and are frequently burdened by high levels of psychosocial stress. However, little is known about how follow-up care after the completed treatment phase can help to improve long-term quality of life. In the context of patient-centred cancer care, considering the survivors' and caregivers' perspectives is an important step toward improving care structures. We therefore explored how lung cancer survivors and their caregivers experience follow-up examinations and their possible psychosocial effects on everyday life in order to shed light on what support is helpful for improving their quality of life. MATERIAL AND METHODS: 25 survivors after curative lung cancer treatment and 17 caregivers underwent a face-to-face semi-structured, audio-recorded interview that was analysed using qualitative content analysis. RESULTS: Especially burdened cancer survivors and caregivers described recurring anxiety before a follow-up appointment influencing their everyday life. At the same time, follow-up care also provided reassurance of still being healthy and helped regain a sense of security and control until the following scan. Despite possible long-term consequences in everyday life, the interviewees reported that the survivors´ psychosocial needs were not explicitly assessed or discussed. Nevertheless, the interviewees indicated that conversations with the physician were important for the success of "good" follow-up care. CONCLUSION: Anxiety surrounding follow-up scans, also known as "scanxiety", is a common problem. In this study, we expanded on previous findings and found a positive aspect of scans, namely regaining a sense of security and control, which can strengthen the psychological well-being of the survivors and their families. To optimize follow-up care and improve the quality of life of lung cancer survivors and caregivers, strategies to integrate psychosocial care, like the introduction of survivorship care plans or increased use of patient-reported outcomes, should be explored in the future.

Influence of the Single Nucleotide Polymorphisms rs12252 and rs34481144 in IFITM3 on the Antibody Response after Vaccination against COVID-19.

The COVID-19 mRNA vaccine is the first mRNA vaccine approved for human administration by both the U.S. Food and Drug Administration and the European Medicines Agency. Studies have shown that the immune response and the decay of immunity after vaccination with the COVID-19 vaccines are variable within a population. Host genetic factors probably contribute to this variability. In this study, we investigated the effect of the single-nucleotide polymorphisms rs12252 and rs34481144 in the interferon-induced transmembrane protein (IFITM) 3 gene on the humoral immune response after vaccination against COVID-19 with mRNA vaccines. Blood samples were collected from 1893 healthcare workers and medical students at multiple time points post-vaccination and antibody titers against the SARS-CoV-2 S1 protein receptor binding domain were determined at all time points. All participants were genotyped for the rs34481144 and rs12252 polymorphisms in the IFITM3 gene. After the second and third vaccinations, antibody titer levels increased at one month and decreased at six months (p < 0.0001) and were higher after the booster vaccination than after the basic immunization (p < 0.0001). Participants vaccinated with mRNA-1273 had a higher humoral immune response than participants vaccinated with BNT162b2. rs12252 had no effect on the antibody response. In contrast, carriers of the GG genotype in rs34481144 vaccinated with BNT162b2 had a lower humoral immune response compared to A allele carriers, which reached statistical significance on the day of the second vaccination (p = 0.03) and one month after the second vaccination (p = 0.04). Further studies on the influence of rs12252 and rs34481144 on the humoral immune response after vaccination against COVID-19 are needed.

Electrolyte imbalance causes suppression of NK and T cell effector function in malignant ascites.

BACKGROUND: Malignant ascites commonly occurs in advanced or recurrent stages of epithelial ovarian cancer during peritoneal carcinomatosis and is correlated with poor prognosis. Due to its complex composition of cellular and acellular components malignant ascites creates a unique tumor microenvironment, which mediates immunosuppression and promotes progression of disease. However, the immunosuppressive mechanisms remain poorly understood. METHODS: In the present study, we explored the antitumor activity of healthy donor NK and T cells directed against ovarian cancer cells in presence of malignant ascites derived from patients with advanced or recurrent peritoneal carcinomatosis. A wide range of methods was used to study the effect of ascites on NK and T cells (FACS, ELISA, EliSpot, qPCR, Live-cell and confocal microscopy, Western blot and electrolyte flux assays). The ascites components were assessed using quantitative analysis (nephelometry, potentiometry and clinical chemistry) and separation methods (dialysis, ultracentrifugal filtration and lipid depletion). RESULTS: Ascites rapidly inhibited NK cell degranulation, tumor lysis, cytokine secretion and calcium signaling. Similarly, target independent NK and T cell activation was impaired in ascites environment. We identified imbalanced electrolytes in ascites as crucial factors causing extensive immunosuppression of NK and T cells. Specifically, high sodium, low chloride and low potassium content significantly suppressed NK-mediated cytotoxicity. Electrolyte imbalance led to changes in transcription and protein expression of electrolyte channels and impaired NK and T cell activation. Selected inhibitors of sodium electrolyte channels restored intracellular calcium flux, conjugation, degranulation and transcript expression of signaling molecules. The levels of ascites-mediated immunosuppression and sodium/chloride/potassium imbalance correlated with poor patient outcome and selected molecular alterations were confirmed in immune cells from ovarian cancer patients. CONCLUSION: Our data suggest a novel electrolyte-based mechanism of immunosuppression in malignant ascites of patients with peritoneal carcinomatosis. We show for the first time that the immunosuppression of NK cytotoxicity in coculture assays is correlated to patient poor survival. Therapeutic application of sodium channel inhibitors may provide new means for restoring immune cell activity in ascites or similar electrolyte imbalanced environments.

Effect of serum creatinine difference between the Jaffe and the enzymatic method on kidney disease detection and staging.

Background: Serum creatinine (SCr), mainly determined by the Jaffe or an enzymatic method, is the central marker to assess kidney function. Deviations between these two methods may affect the diagnosis and staging of acute kidney injury (AKI) and chronic kidney disease (CKD). Methods: The results of the first parallel SCr measurement (Jaffe and enzymatic method) of adult in- and outpatients in the same serum sample at the University Hospital Essen (Essen, Germany) between 2020-2022 were retrospectively evaluated. A Bland-Altman plot with 95% limits of agreement (LoAs) was used to assess the difference between the Jaffe and the enzymatic SCr (eSCr) method. We used the 2009 Chronic Kidney Disease Epidemiology Collaboration equation for determination of estimated glomerular filtration rate (eGFR) according to the Kidney Disease: Improving Global Outcomes guidelines. Results: A total of 41 144 parallel SCr measurements were evaluated. On average, Jaffe SCr was 0.07 mg/dl higher than eSCr (LoA -0.12; 0.25 mg/dl). In 19% of all cases there was a different CKD stage when comparing eGFR between both SCr methods, of which 98% resulted in a more severe CKD stage determined with Jaffe SCr. In 1.6% of all cases Jaffe SCr was ≥0.3 mg/dl higher than eSCr. Conclusion: The present study showed that methods of SCr measurement may affect both the diagnosis and staging of AKI and CKD. This must be taken into account when interpreting measurements of renal function in everyday clinical practice, but also when planning and comparing studies on renal diseases. One should therefore stay with one method for SCr measurement, preferably with the enzymatic method.

Individuals With Weaker Antibody Responses After Booster Immunization Are Prone to Omicron Breakthrough Infections.

Background: Despite the high level of protection against severe COVID-19 provided by the currently available vaccines some breakthrough infections occur. Until now, there is no information whether a potential risk of a breakthrough infection can be inferred from the level of antibodies after booster vaccination. Methods: Levels of binding antibodies and neutralization capacity after the first, one and six month after the second, and one month after the third (booster) vaccination against COVID-19 were measured in serum samples from 1391 healthcare workers at the University Hospital Essen. Demographics, vaccination scheme, pre-infection antibody titers and neutralization capacity were compared between individuals with and without breakthrough infections. Results: The risk of developing an Omicron breakthrough infection was independent of vaccination scheme, sex, body mass index, smoking status or pre-existing conditions. In participants with low pre-infection anti-spike antibodies (≤ 2641.0 BAU/ml) and weaker neutralization capacity (≤ 65.9%) against Omicron one month after the booster vaccination the risk for developing an Omicron infection was 10-fold increased (P = 0.001; 95% confidence interval, 2.36 - 47.55). Conclusion: Routine testing of anti-SARS-CoV-2 IgG antibodies and surrogate virus neutralization can quantify vaccine-induced humoral immune response and may help to identify subjects who are at risk for a breakthrough infection. The establishment of thresholds for SARS-CoV-2 IgG antibody levels identifying "non"-, "low" and "high"-responders may be used as an indication for re-vaccination.

Larix species range dynamics in Siberia since the Last Glacial captured from sedimentary ancient DNA.

Climate change is expected to cause major shifts in boreal forests which are in vast areas of Siberia dominated by two species of the deciduous needle tree larch (Larix). The species differ markedly in their ecosystem functions, thus shifts in their respective ranges are of global relevance. However, drivers of species distribution are not well understood, in part because paleoecological data at species level are lacking. This study tracks Larix species distribution in time and space using target enrichment on sedimentary ancient DNA extracts from eight lakes across Siberia. We discovered that Larix sibirica, presently dominating in western Siberia, likely migrated to its northern distribution area only in the Holocene at around 10,000 years before present (ka BP), and had a much wider eastern distribution around 33 ka BP. Samples dated to the Last Glacial Maximum (around 21 ka BP), consistently show genotypes of L. gmelinii. Our results suggest climate as a strong determinant of species distribution in Larix and provide temporal and spatial data for species projection in a changing climate.

Universally applicable model for the quantitative determination of lake sediment composition using fourier transform infrared spectroscopy.

Fourier transform infrared spectroscopy (FTIRS) can provide detailed information on organic and minerogenic constituents of sediment records. Based on a large number of sediment samples of varying age (0-340,000 yrs) and from very diverse lake settings in Antarctica, Argentina, Canada, Macedonia/Albania, Siberia, and Sweden, we have developed universally applicable calibration models for the quantitative determination of biogenic silica (BSi; n = 816), total inorganic carbon (TIC; n = 879), and total organic carbon (TOC; n = 3164) using FTIRS. These models are based on the differential absorbance of infrared radiation at specific wavelengths with varying concentrations of individual parameters, due to molecular vibrations associated with each parameter. The calibration models have low prediction errors and the predicted values are highly correlated with conventionally measured values (R = 0.94-0.99). Robustness tests indicate the accuracy of the newly developed FTIRS calibration models is similar to that of conventional geochemical analyses. Consequently FTIRS offers a useful and rapid alternative to conventional analyses for the quantitative determination of BSi, TIC, and TOC. The rapidity, cost-effectiveness, and small sample size required enables FTIRS determination of geochemical properties to be undertaken at higher resolutions than would otherwise be possible with the same resource allocation, thus providing crucial sedimentological information for climatic and environmental reconstructions.

Lake Ohrid's tephrochronological dataset reveals 1.36 Ma of Mediterranean explosive volcanic activity.

Tephrochronology relies on the availability of the stratigraphical, geochemical and geochronological datasets of volcanic deposits, three preconditions which are both often only fragmentary accessible. This study presents the tephrochronological dataset from the Lake Ohrid (Balkans) sediment succession continuously reaching back to 1.36 Ma. 57 tephra layers were investigated for their morphological appearance, geochemical fingerprint, and (chrono-)stratigraphic position. Glass fragments of tephra layers were analyzed for their major element composition using Energy-Dispersive-Spectroscopy and Wavelength-Dispersive Spectroscopy and for their trace element composition by Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry. Radiometric dated equivalents of 16 tephra layers and orbital tuning of geochemical proxy data provided the basis for the age-depth model of the Lake Ohrid sediment succession. The age-depth model, in turn, provides ages for unknown or undated tephra layers. This dataset forms the basis for a regional stratigraphic framework and provides insights into the central Mediterranean explosive volcanic activity during the last 1.36 Ma.

Nusinersen treatment in adult patients with spinal muscular atrophy: a safety analysis of laboratory parameters.

BACKGROUND: Nusinersen is an intrathecally administered antisense oligonucleotide (ASO) that improves motor function in patients with spinal muscular atrophy (SMA). In addition to efficacy, the safety of a therapy is the decisive factor for the success of the treatment. For some ASOs, various organ toxicities have been described, such as thrombocytopenia, renal and liver impairment, or coagulation abnormalities. However, systematic data on laboratory parameters under treatment with nusinersen are mainly available from studies in infants and children. Therefore, our aim was to assess the safety of nusinersen therapy in adult SMA patients. METHODS: Laboratory data from 404 nusinersen injections performed in 50 adult patients with SMA type 2 and type 3 were retrospectively analyzed. RESULTS: The total observation period was 76.9 patient-years, and patients received up to 12 injections. Our data provides no new safety concerns. In cerebrospinal fluid (CSF), the mean white blood cell count and lactate remained stable over time. Total CSF protein increased by 2.9 mg/dL. No change in mean platelet count was observed under therapy. Only one patient showed sporadic mild thrombocytopenia. Coagulation parameters and inflammatory markers were stable. The mean creatinine level decreased by 0.09 mg/dL. Analysis of mean liver enzyme levels revealed no relevant changes during treatment. CONCLUSION: Our data demonstrate a favorable safety profile of nusinersen therapy in adult SMA patients under longer-term "real-world" conditions. In particular, we found no evidence of clinically relevant platelet declines, coagulopathies, or renal or hepatic organ toxicities, which are common concerns with the use of ASOs.

Metabolic requirements of NK cells during the acute response against retroviral infection.

Natural killer (NK) cells are important early responders against viral infections. Changes in metabolism are crucial to fuel NK cell responses, and altered metabolism is linked to NK cell dysfunction in obesity and cancer. However, very little is known about the metabolic requirements of NK cells during acute retroviral infection and their importance for antiviral immunity. Here, using the Friend retrovirus mouse model, we show that following infection NK cells increase nutrient uptake, including amino acids and iron, and reprogram their metabolic machinery by increasing glycolysis and mitochondrial metabolism. Specific deletion of the amino acid transporter Slc7a5 has only discrete effects on NK cells, but iron deficiency profoundly impaires NK cell antiviral functions, leading to increased viral loads. Our study thus shows the requirement of nutrients and metabolism for the antiviral activity of NK cells, and has important implications for viral infections associated with altered iron levels such as HIV and SARS-CoV-2.

Weak Influence of Paleoenvironmental Conditions on the Subsurface Biosphere of Lake Ohrid over the Last 515 ka.

Lacustrine sediments are widely used to investigate the impact of climatic change on biogeochemical cycling. In these sediments, subsurface microbial communities are major actors of this cycling but can also affect the sedimentary record and overprint the original paleoenvironmental signal. We therefore investigated the subsurface microbial communities of the oldest lake in Europe, Lake Ohrid (North Macedonia, Albania), to assess the potential connection between microbial diversity and past environmental change using 16S rRNA gene sequences. Along the upper ca. 200 m of the DEEP site sediment record spanning ca. 515 thousand years (ka), our results show that Atribacteria, Bathyarchaeia and Gammaproteobacteria structured the community independently from each other. Except for the latter, these taxa are common in deep lacustrine and marine sediments due to their metabolic versatility adapted to low energy environments. Gammaproteobacteria were often co-occurring with cyanobacterial sequences or soil-related OTUs suggesting preservation of ancient DNA from the water column or catchment back to at least 340 ka, particularly in dry glacial intervals. We found significant environmental parameters influencing the overall microbial community distribution, but no strong relationship with given phylotypes and paleoclimatic signals or sediment age. Our results support a weak recording of early diagenetic processes and their actors by bulk prokaryotic sedimentary DNA in Lake Ohrid, replaced by specialized low-energy clades of the deep biosphere and a marked imprint of erosional processes on the subsurface DNA pool of Lake Ohrid.

Deep drilling reveals massive shifts in evolutionary dynamics after formation of ancient ecosystem.

The scarcity of high-resolution empirical data directly tracking diversity over time limits our understanding of speciation and extinction dynamics and the drivers of rate changes. Here, we analyze a continuous species-level fossil record of endemic diatoms from ancient Lake Ohrid, along with environmental and climate indicator time series since lake formation 1.36 million years (Ma) ago. We show that speciation and extinction rates nearly simultaneously decreased in the environmentally dynamic phase after ecosystem formation and stabilized after deep-water conditions established in Lake Ohrid. As the lake deepens, we also see a switch in the macroevolutionary trade-off, resulting in a transition from a volatile assemblage of short-lived endemic species to a stable community of long-lived species. Our results emphasize the importance of the interplay between environmental/climate change, ecosystem stability, and environmental limits to diversity for diversification processes. The study also provides a new understanding of evolutionary dynamics in long-lived ecosystems.

Micro- and macrorheological properties of isotropically cross-linked actin networks.

Cells make use of semiflexible biopolymers such as actin or intermediate filaments to control their local viscoelastic response by dynamically adjusting the concentration and type of cross-linking molecules. The microstructure of the resulting networks mainly determines their mechanical properties. It remains an important challenge to relate structural transitions to both the molecular properties of the cross-linking molecules and the mechanical response of the network. This can be achieved best by well defined in vitro model systems in combination with microscopic techniques. Here, we show that with increasing concentrations of the cross-linker heavy meromyosin, a transition in the mechanical network response occurs. At low cross-linker densities the network elasticity is dominated by the entanglement length l(e) of the polymer, whereas at high heavy meromyosin densities the cross-linker distance l(c) determines the elastic behavior. Using microrheology the formation of heterogeneous networks is observed at low cross-linker concentrations. Micro- and macrorheology both report the same transition to a homogeneous cross-linked phase. This transition is set by a constant average cross-linker distance l(c) approximately 15 microm. Thus, the micro- and macromechanical properties of isotropically cross-linked in vitro actin networks are determined by only one intrinsic network parameter.

Methyl group dynamics in glassy, polycrystalline, and liquid coenzyme Q10 studied by quasielastic neutron scattering.

The methyl group rotation of coenzyme Q(10) confined in nanosized droplets was studied using quasielastic neutron scattering (QENS). Q(10) as an oligoisoprene derivative with ten isoprene units can easily be supercooled in nanodroplets. Fixed window scans and QENS spectra at several temperatures of glassy Q(10) were recorded to study the methyl group rotation which can be described by a logarithmic Gaussian distribution of hopping rates for temperatures below the glass transition temperature (T(g) approximately 200 K). A mean activation energy of 4.8 kJ/mol with a distribution width of 2.1 kJ/mol was obtained from the evaluation of the QENS spectra. A corresponding analysis of a fixed window scan yielded an average activation energy of 5.1 kJ/mol with a distribution width of 1.8 kJ/mol. The results are compared and discussed with those of chain deuterated polyisoprene-d(5). For polycrystalline Q(10), the QENS spectra could be described by the same model yielding a similar average activation energy as found for glassy Q(10). However, no temperature dependence of the distribution width was observed. Based on the performed low-temperature measurements, the correlation times for the methyl group rotation were extrapolated to temperatures of liquid Q(10). The complex dynamics of liquid Q(10) could be described by a model yielding an apparent diffusion coefficient, the jump rate of the methyl groups, as well as an overall molecular rotational diffusion coefficient. The correlation times of the methyl group rotation in liquid Q(10) at a given temperature T(0) coincide with values determined in the glassy phase and extrapolated to T(0).