The circadian clock time tunes axonal regeneration.

Nerve injuries cause permanent neurological disability due to limited axonal regeneration. Injury-dependent and -independent mechanisms have provided important insight into neuronal regeneration, however, common denominators underpinning regeneration remain elusive. A comparative analysis of transcriptomic datasets associated with neuronal regenerative ability revealed circadian rhythms as the most significantly enriched pathway. Subsequently, we demonstrated that sensory neurons possess an endogenous clock and that their regenerative ability displays diurnal oscillations in a murine model of sciatic nerve injury. Consistently, transcriptomic analysis showed a time-of-day-dependent enrichment for processes associated with axonal regeneration and the circadian clock. Conditional deletion experiments demonstrated that Bmal1 is required for neuronal intrinsic circadian regeneration and target re-innervation. Lastly, lithium enhanced nerve regeneration in wild-type but not in clock-deficient mice. Together, these findings demonstrate that the molecular clock fine-tunes the regenerative ability of sensory neurons and propose compounds affecting clock pathways as a novel approach to nerve repair.

CT after interhospital transfer in acute ischemic stroke: Imaging findings and impact of prior intravenous contrast administration.

Objectives: Large vessel occlusion (LVO) stroke patients routinely undergo interhospital transfer to endovascular thrombectomy capable centers. Imaging is often repeated with residual intravenous (IV) iodine contrast at post-transfer assessment. We determined imaging findings and the impact of residual contrast on secondary imaging. Anterior circulation LVO stroke patients were selected out of a consecutive cohort. Directly admitted patients were contrast naïve, and transferred patients had previously received IV iodine contrast for stroke assessment at the referring hospital. Two independent readers rated the visibility of residual contrast on non-contrast computed tomography (CT) after transfer and assessed the hyperdense vessel sign. Multivariate linear regression analysis was used to investigate the association of the Alberta Stroke Program Early CT score (ASPECTS) with prior contrast administration, time from symptom onset (TFSO), and CTP ischemic core volume in both directly admitted and transferred patients. Results: We included 161 patients, with 62 (39%) transferred and 99 (62%) directly admitted patients. Compared between these groups, transferred patients had a longer TFSO-to-imaging at our institution (median: 212 vs. 75 min, p < 0.001) and lower ASPECTS (median: 8 vs. 9, p < 0.001). Regression analysis presented an independent association of ASPECTS with prior contrast administration (ß = -0.25, p = 0.004) but not with TFSO (ß = -0.03, p = 0.65). Intergroup comparison between transferred and directly admitted patients pointed toward a stronger association between ASPECTS and CTP ischemic core volume in transferred patients (ß = -0.39 vs. ß = -0.58, p = 0.06). Detectability of the hyperdense vessel sign was substantially lower after transfer (66 vs. 10%, p < 0.001). Conclusion: Imaging alterations due to residual IV contrast are frequent in clinical practice and render the hyperdense vessel sign largely indetectable. Larger studies are needed to clarify the influence on the association between ASPECTS and ischemic core.

Decomposing Acute Symptom Severity in Large Vessel Occlusion Stroke: Association With Multiparametric CT Imaging and Clinical Parameters.

Background and Purpose: Acute ischemic stroke of the anterior circulation due to large vessel occlusion (LVO) is a multifactorial process, which causes neurologic symptoms of different degree. Our aim was to examine the impact of neuromorphologic and vascular correlates as well as clinical factors on acute symptom severity in LVO stroke. Methods: We selected LVO stroke patients with known onset time from a consecutive cohort which underwent multiparametric CT including non-contrast CT, CT angiography and CT perfusion (CTP) before thrombectomy. Software-based quantification was used to calculate CTP total ischemic and ischemic core volume. Symptom severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) upon admission. Multivariable regression analysis was performed to determine independent associations of admission NIHSS with imaging and clinical parameters. Receiver operating characteristics (ROC) analyses were used to examine performance of imaging parameters to classify symptom severity. Results: We included 142 patients. Linear and ordinal regression analyses for NIHSS and NIHSS severity groups identified significant associations for total ischemic volume [ß = 0.31, p = 0.01; Odds ratio (OR) = 1.11, 95%-confidence-interval (CI): 1.02-1.19], clot burden score (ß = -0.28, p = 0.01; OR = 0.76, 95%-CI: 0.64-0.90) and age (ß = 0.17, p = 0.04). No association was found for ischemic core volume, stroke side, collaterals and time from onset. Stroke topography according to the Alberta Stroke Program CT Score template did not display significant influence after correction for multiple comparisons. AUC for classification of the NIHSS threshold ≥6 by total ischemic volume was 0.81 (p < 0.001). Conclusions: We determined total ischemic volume, clot burden and age as relevant drivers for baseline NIHSS in acute LVO stroke. This suggests that not only mere volume but also degree of occlusion influences symptom severity. Use of imaging parameters as surrogate for baseline NIHSS reached limited performance underlining the need for combined clinical and imaging assessment in acute stroke management.

Overlap of NatA and IAP substrates implicates N-terminal acetylation in protein stabilization.

SMAC/DIABLO and HTRA2 are mitochondrial proteins whose amino-terminal sequences, known as inhibitor of apoptosis binding motifs (IBMs), bind and activate ubiquitin ligases known as inhibitor of apoptosis proteins (IAPs), unleashing a cell's apoptotic potential. IBMs comprise a four-residue, loose consensus sequence, and binding to IAPs requires an unmodified amino terminus. Closely related, IBM-like N termini are present in approximately 5% of human proteins. We show that suppression of the N-alpha-acetyltransferase NatA turns these cryptic IBM-like sequences into very efficient IAP binders in cell lysates and in vitro and ultimately triggers cellular apoptosis. Thus, amino-terminal acetylation of IBM-like motifs in NatA substrates shields them from IAPs. This previously unrecognized relationship suggests that amino-terminal acetylation is generally protective against protein degradation in human cells. It also identifies IAPs as agents of a general quality control mechanism targeting unacetylated rogues in metazoans.

Complications of left ventricular assist devices causing high urgency status on waiting list: impact on outcome after heart transplantation.

AIMS: Heart transplantation (HTx) represents optimal care for advanced heart failure. Left ventricular assist devices (LVADs) are often needed as a bridge-to-transplant (BTT) therapy to support patients during the wait for a donor organ. Prolonged support increases the risk for LVAD complications that may affect the outcome after HTx. METHODS AND RESULTS: A total of 342 patients undergoing HTx after LVAD as BTT in a 10-year period in two German high-volume HTx centres were retrospectively analysed. While 73 patients were transplanted without LVAD complications and with regular waiting list status (T, n = 73), the remaining 269 patients were transplanted with high urgency status (HU) and further divided with regard to the observed leading LVAD complications (infection: HU1, n = 91; thrombosis: HU2, n = 32; stroke: HU3, n = 38; right heart failure: HU4, n = 41; arrhythmia: HU5, n = 23; bleeding: HU6, n = 18; device malfunction: HU7, n = 26). Postoperative hospitalization was prolonged in patients with LVAD complications. Analyses of perioperative morbidity revealed no differences regarding primary graft dysfunction, renal failure, and neurological events except postoperative infections. Short-term survival, as well as Kaplan-Meier survival analysis, indicated comparable results between the different study groups without disadvantages for patients with LVAD complications. CONCLUSIONS: Left ventricular assist device therapy can impair the outcome after HTx. However, the occurrence of LVAD complications may not impact on outcome after HTx. Thus, we cannot support the prioritization or discrimination of HTx candidates according to distinct mechanical circulatory support-associated complications. Future allocation strategies have to respect that device-related complications may define urgency but do not impact on the outcome after HTx.

Diaschisis revisited: quantitative evaluation of thalamic hypoperfusion in anterior circulation stroke.

PURPOSE: Ipsilateral thalamic diaschisis (ITD) refers to the phenomenon of thalamic hypoperfusion or hypometabolism due to a distant cerebral injury. To further investigate the characteristics and spectrum of ITD, we analyzed quantitative measurements of thalamic hypoperfusion in acute anterior circulation stroke. METHODS: We selected consecutive patients with large-vessel occlusion (LVO) anterior circulation stroke and available CT perfusion (CTP) examination on admission who underwent endovascular thrombectomy. Thalamic perfusion parameters on CTP were tested between ipsi- and contralesional thalamus and ischemic territory. Values were compared with thresholds from CTP analysis software. Associations of thalamic perfusion parameters with acute imaging and clinical data were determined in uni- and multivariate logistic regression analyses. RESULTS: Ninety-nine patients were included. All perfusion parameters indicated significant non-ischemic hypoperfusion of the thalamus, not reaching the levels of ischemia in the middle cerebral artery territory due to LVO (all p < 0.002). Multiple perfusion parameters exhibited significant association with ischemic lesion extent (relative cerebral blood flow [CBF]: ß =  - 0.23, p = 0.022; Δtime to drain: ß = 0.33, p < 0.001; ΔTmax: ß =  - 0.36, p < 0.001) and involvement of the Lentiform Nucleus (Δmean transit time: ß = 0.64, p = 0.04; Δtime to drain: ß = 0.81, p = 0.01; ΔTmax: ß =  - 0.82, p = 0.01). Symptom severity on admission exhibited minor significant association with reduction of thalamic CBF in uncorrected analysis (Odds ratio: 0.05, p = 0.049), but short- and long-term outcomes were unaffected by perfusion status. ITD reached guideline-based software-threshold levels in only one patient. CONCLUSIONS: ITD in acute stroke is a non-binary phenomenon affected by lesion extent and involvement of the lentiform nucleus. We found uncorrected association of ITD with early clinical presentation, but no association with short- or long-term outcome was evident. Relevant misclassification of ITD by guideline-based CTP software was not indicated, which needs further dedicated testing.

Scalable Synthesis of Microsized, Nanocrystalline Zn0.9 Fe0.1 O-C Secondary Particles and Their Use in Zn0.9 Fe0.1 O-C/LiNi0.5 Mn1.5 O4 Lithium-Ion Full Cells.

Conversion/alloying materials (CAMs) are a potential alternative to graphite as Li-ion anodes, especially for high-power performance. The so far most investigated CAM is carbon-coated Zn0.9 Fe0.1 O, which provides very high specific capacity of more than 900 mAh g-1 and good rate capability. Especially for the latter the optimal particle size is in the nanometer regime. However, this leads to limited electrode packing densities and safety issues in large-scale handling and processing. Herein, a new synthesis route including three spray-drying steps that results in the formation of microsized, spherical secondary particles is reported. The resulting particles with sizes of 10-15 µm are composed of carbon-coated Zn0.9 Fe0.1 O nanocrystals with an average diameter of approximately 30-40 nm. The carbon coating ensures fast electron transport in the secondary particles and, thus, high rate capability of the resulting electrodes. Coupling partially prelithiated, carbon-coated Zn0.9 Fe0.1 O anodes with LiNi0.5 Mn1.5 O4 cathodes results in cobalt-free Li-ion cells delivering a specific energy of up to 284 Wh kg-1 (at 1 C rate) and power of 1105 W kg-1 (at 3 C) with remarkable energy efficiency (>93 % at 1 C and 91.8 % at 3 C).

DHHC7-mediated palmitoylation of the accessory protein barttin critically regulates the functions of ClC-K chloride channels.

Barttin is the accessory subunit of the human ClC-K chloride channels, which are expressed in both the kidney and inner ear. Barttin promotes trafficking of the complex it forms with ClC-K to the plasma membrane and is involved in activating this channel. Barttin undergoes post-translational palmitoylation that is essential for its functions, but the enzyme(s) catalyzing this post-translational modification is unknown. Here, we identified zinc finger DHHC-type containing 7 (DHHC7) protein as an important barttin palmitoyl acyltransferase, whose depletion affected barttin palmitoylation and ClC-K-barttin channel activation. We investigated the functional role of barttin palmitoylation in vivo in Zdhhc7-/- mice. Although palmitoylation of barttin in kidneys of Zdhhc7-/- animals was significantly decreased, it did not pathologically alter kidney structure and functions under physiological conditions. However, when Zdhhc7-/- mice were fed a low-salt diet, they developed hyponatremia and mild metabolic alkalosis, symptoms characteristic of human Bartter syndrome (BS) type IV. Of note, we also observed decreased palmitoylation of the disease-causing R8L barttin variant associated with human BS type IV. Our results indicate that dysregulated DHHC7-mediated barttin palmitoylation appears to play an important role in chloride channel dysfunction in certain BS variants, suggesting that targeting DHHC7 activity may offer a potential therapeutic strategy for reducing hypertension.

Simplified Protocol for Cross-linking Mass Spectrometry Using the MS-Cleavable Cross-linker DSBU with Efficient Cross-link Identification.

Chemical cross-linking combined with mass spectrometry (MS) is a powerful approach to identify and map protein-protein interactions. Its applications support computational modeling of three-dimensional structures and complement classical structural methodologies such as X-ray crystallography, NMR spectroscopy, and electron microscopy (EM). A plethora of cross-linkers, MS methods, and data analysis programs have been developed, but due to their methodological complexity application is currently reserved for specialized mass spectrometry laboratories. Here, we present a simplified single-step purification protocol that results in improved identifications of cross-linked peptides. We describe an easy-to-follow pipeline that combines the MS-cleavable cross-linker DSBU (disuccinimidyl dibutyric urea), a Q-Exactive mass spectrometer, and the dedicated software MeroX for data analysis to make cross-linking MS accessible to structural biology and biochemistry laboratories. In experiments focusing on kinetochore subcomplexes containing 4-10 subunits (so-called KMN network), one-step peptide purification, and enrichment by size-exclusion chromatography yielded identification of 135-228 non-redundant cross-links (577-820 cross-linked peptides) from each experiment. Notably, half of the non-redundant cross-links identified were not lysine-lysine cross-links and involved side chains with hydroxy groups. The new pipeline has a comparable potential toward the identification of protein-protein interactions as previously used pipelines based on isotope-labeled cross-linkers. A newly identified cross-link enabled us to improve our 3D-model of the KMN, emphasizing the power of cross-linking data for evaluation of low-resolution EM maps. In sum, our optimized experimental scheme represents a viable shortcut toward obtaining reliable cross-link data sets.

Low-Polarization Lithium-Oxygen Battery Using [DEME][TFSI] Ionic Liquid Electrolyte.

The room-temperature molten salt mixture of N,N-diethyl-N-(2-methoxyethyl)-N-methylammonium bis(trifluoromethanesulfonyl) imide ([DEME][TFSI]) and lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) salt is herein reported as electrolyte for application in Li-O2 batteries. The [DEME][TFSI]-LiTFSI solution is studied in terms of ionic conductivity, viscosity, electrochemical stability, and compatibility with lithium metal at 30 °C, 40 °C, and 60 °C. The electrolyte shows suitable properties for application in Li-O2 battery, allowing a reversible, low-polarization discharge-charge performance with a capacity of about 13 Ah g-1carbon in the positive electrode and coulombic efficiency approaching 100 %. The reversibility of the oxygen reduction reaction (ORR)/oxygen evolution reaction (OER) is demonstrated by ex situ XRD and SEM studies. Furthermore, the study of the cycling behavior of the Li-O2 cell using the [DEME][TFSI]-LiTFSI electrolyte at increasing temperatures (from 30 to 60 °C) evidences enhanced energy efficiency together with morphology changes of the deposited species at the working electrode. In addition, the use of carbon-coated Zn0.9 Fe0.1 O (TMO-C) lithium-conversion anode in an ionic-liquid-based Li-ion/oxygen configuration is preliminarily demonstrated.

Structural and Electrochemical Characterization of Zn1-xFexO-Effect of Aliovalent Doping on the Li⁺ Storage Mechanism.

In order to further improve the energy and power density of state-of-the-art lithium-ion batteries (LIBs), new cell chemistries and, therefore, new active materials with alternative storage mechanisms are needed. Herein, we report on the structural and electrochemical characterization of Fe-doped ZnO samples with varying dopant concentrations, potentially serving as anode for LIBs (Rechargeable lithium-ion batteries). The wurtzite structure of the Zn1-xFexO samples (with x ranging from 0 to 0.12) has been refined via the Rietveld method. Cell parameters change only slightly with the Fe content, whereas the crystallinity is strongly affected, presumably due to the presence of defects induced by the Fe3+ substitution for Zn2+. XANES (X-ray absorption near edge structure) data recorded ex situ for Zn0.9Fe0.1O electrodes at different states of charge indicated that Fe, dominantly trivalent in the pristine anode, partially reduces to Fe2+ upon discharge. This finding was supported by a detailed galvanostatic and potentiodynamic investigation of Zn1-xFexO-based electrodes, confirming such an initial reduction of Fe3+ to Fe2+ at potentials higher than 1.2 V (vs. Li⁺/Li) upon the initial lithiation, i.e., discharge. Both structural and electrochemical data strongly suggest the presence of cationic vacancies at the tetrahedral sites, induced by the presence of Fe3+ (i.e., one cationic vacancy for every two Fe3+ present in the sample), allowing for the initial Li⁺ insertion into the ZnO lattice prior to the subsequent conversion and alloying reaction.

Is the Solid Electrolyte Interphase an Extra-Charge Reservoir in Li-Ion Batteries?

Advanced metal oxide electrodes in Li-ion batteries usually show reversible capacities exceeding the theoretically expected ones. Despite many studies and tentative interpretations, the origin of this extra-capacity is not assessed yet. Lithium storage can be increased through different chemical processes developing in the electrodes during charging cycles. The solid electrolyte interface (SEI), formed already during the first lithium uptake, is usually considered to be a passivation layer preventing the oxidation of the electrodes while not participating in the lithium storage process. In this work, we combine high resolution soft X-ray absorption spectroscopy with tunable probing depth and photoemission spectroscopy to obtain profiles of the surface evolution of a well-known prototype conversion-alloying type mixed metal oxide (carbon coated ZnFe2O4) electrode. We show that a partially reversible layer of alkyl lithium carbonates is formed (∼5-7 nm) at the SEI surface when reaching higher Li storage levels. This layer acts as a Li reservoir and seems to give a significant contribution to the extra-capacity of the electrodes. This result further extends the role of the SEI layer in the functionality of Li-ion batteries.

Facile hybridization of Ni@Fe2O3 superparticles with functionalized reduced graphene oxide and its application as anode material in lithium-ion batteries.

In our present work we developed a novel graphene wrapping approach of Ni@Fe2O3 superparticles, which can be extended as a concept approach for other nanomaterials as well. It uses sulfonated reduced graphene oxide, but avoids thermal treatments and use of toxic agents like hydrazine for its reduction. The modification of graphene oxide is achieved by the introduction of sulfate groups accompanied with reduction and elimination reactions, due to the treatment with oleum. The successful wrapping of nanoparticles is proven by energy dispersive X-ray spectroscopy, high-resolution transmission electron microscopy and Raman spectroscopy. The developed composite material shows strongly improved performance as anode material in lithium-ion batteries (compared to unwrapped Ni@Fe2O3) as it offers a reversible capacity of 1051mAhg(-1) after 40 cycles at C/20, compared with 460mAhg(-1) for unwrapped Ni@Fe2O3. The C rate capability is also improved by the wrapping approach, as specific capacities for wrapped particles are about twice of those offered by unwrapped particles. Additionally, the benefit for the use of the advanced superparticle morphology is demonstrated by comparing wrapped Ni@Fe2O3 particles with wrapped Fe2O3 nanorice.

Cleavage of Hyaluronan and CD44 Adhesion Molecule Regulate Astrocyte Morphology via Rac1 Signalling.

Communication of cells with their extracellular environment is crucial to fulfill their function in physiological and pathophysiological conditions. The literature data provide evidence that such a communication is also important in case of astrocytes. Mechanisms that contribute to the interaction between astrocytes and extracellular matrix (ECM) proteins are still poorly understood. Hyaluronan is the main component of ECM in the brain, where its major receptor protein CD44 is expressed by a subset of astrocytes. Considering the fact that functions of astrocytes are tightly coupled with changes in their morphology (e.g.: glutamate clearance in the synaptic cleft, migration, astrogliosis), we investigated the influence of hyaluronan cleavage by hyaluronidase, knockdown of CD44 by specific shRNA and CD44 overexpression on astrocyte morphology. Our results show that hyaluronidase treatment, as well as knockdown of CD44, in astrocytes result in a "stellate"-like morphology, whereas overexpression of CD44 causes an increase in cell body size and changes the shape of astrocytes into flattened cells. Moreover, as a dynamic reorganization of the actin cytoskeleton is supposed to be responsible for morphological changes of cells, and this reorganization is controlled by small GTPases of the Rho family, we hypothesized that GTPase Rac1 acts as a downstream effector for hyaluronan and CD44 in astrocytes. We used FRET-based biosensor and a dominant negative mutant of Rac1 to investigate the involvement of Rac1 activity in hyaluronidase- and CD44-dependent morphological changes of astrocytes. Both, hyaluronidase treatment and knockdown of CD44, enhances Rac1 activity while overexpression of CD44 reduces the activity state in astrocytes. Furthermore, morphological changes were blocked by specific inhibition of Rac1 activity. These findings indicate for the first time that regulation of Rac1 activity is responsible for hyaluronidase and CD44-driven morphological changes of astrocytes.

A Lithium-Ion Battery with Enhanced Safety Prepared using an Environmentally Friendly Process.

A new lithium-ion battery chemistry is presented based on a conversion-alloying anode material, a carbon-coated Fe-doped ZnO (TMO-C), and a LiNi1/3 Mn1/3 Co1/3 O2 (NMC) cathode. Both electrodes were fabricated using an environmentally friendly cellulose-based binding agent. The performance of the new lithium-ion battery was evaluated with a conventional, carbonate-based electrolyte (ethylene carbonate:diethyl carbonate-1 m lithium hexafluorophosphate, EC:DEC 1 m LiPF6 ) and an ionic liquid (IL)-based electrolyte (N-butyl-N-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide-0.2 m lithium bis(trifluoromethanesulfonyl)imide, Pyr14 TFSI 0.2 m LiTFSI), respectively. Galvanostatic charge/discharge tests revealed a reduced rate capability of the TMO-C/Pyr14 TFSI 0.2 m LiTFSI/NMC full-cell compared to the organic electrolyte, but the coulombic efficiency was significantly enhanced. Moreover, the IL-based electrolyte substantially improves the safety of the system due to a higher thermal stability of the formed anodic solid electrolyte interphase and the IL electrolyte itself. While the carbonate-based electrolyte shows sudden degradation reactions, the IL exhibits a slowly increasing heat flow, which does not constitute a serious safety risk.

In†Situ Coating of Li[Ni0.33 Mn0.33 Co0.33 ]O2 Particles to Enable Aqueous Electrode Processing.

The aqueous processing of lithium-ion battery (LIB) electrodes has the potential to notably decrease the battery processing costs and paves the way for a sustainable and environmentally benign production (and recycling) of electrochemical energy storage devices. Although this concept has already been adopted for the industrial production of LIB graphite anodes, the performance decay of cathode electrodes based on transition metal oxides processed in aqueous environments is still an open issue. In this study, we show that the addition of small quantities of phosphoric acid into the cathodic slurry yields Li[Ni0.33 Mn0.33 Co0.33 ]O2 electrodes that have an outstanding electrochemical performance in lithium-ion cells.

A Long-Life Lithium Ion Battery with Enhanced Electrode/Electrolyte Interface by Using an Ionic Liquid Solution.

In this paper, we report an advanced long-life lithium ion battery, employing a Pyr14 TFSI-LiTFSI non-flammable ionic liquid (IL) electrolyte, a nanostructured tin carbon (Sn-C) nanocomposite anode, and a layered LiNi1/3 Co1/3 Mn1/3 O2 (NMC) cathode. The IL-based electrolyte is characterized in terms of conductivity and viscosity at various temperatures, revealing a Vogel-Tammann-Fulcher (VTF) trend. Lithium half-cells employing the Sn-C anode and NMC cathode in the Pyr14 TFSI-LiTFSI electrolyte are investigated by galvanostatic cycling at various temperatures, demonstrating the full compatibility of the electrolyte with the selected electrode materials. The NMC and Sn-C electrodes are combined into a cathode-limited full cell, which is subjected to prolonged cycling at 40 °C, revealing a very stable capacity of about 140 mAh g(-1) and retention above 99 % over 400 cycles. The electrode/electrolyte interface is further characterized through a combination of electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM) investigations upon cell cycling. The remarkable performances reported here definitively indicate that IL-based lithium ion cells are suitable batteries for application in electric vehicles.

In situ Raman spectroscopy of carbon-coated ZnFe2O4 anode material in Li-ion batteries - investigation of SEI growth.

The (de)lithiation process of carbon-coated ZnFe2O4 has been investigated by in situ Raman spectroscopy. Solid electrolyte interphase (SEI) products were detected. Their detection may result from a temporary surface enhancement Raman effect from Zn nanoparticles formed in the conversion reaction at a potential that coincides with SEI formation.

Eco-friendly Energy Storage System: Seawater and Ionic Liquid Electrolyte.

As existing battery technologies struggle to meet the requirements for widespread use in the field of large-scale energy storage, novel concepts are urgently needed concerning batteries that have high energy densities, low costs, and high levels of safety. Here, a novel eco-friendly energy storage system (ESS) using seawater and an ionic liquid is proposed for the first time; this represents an intermediate system between a battery and a fuel cell, and is accordingly referred to as a hybrid rechargeable cell. Compared to conventional organic electrolytes, the ionic liquid electrolyte significantly enhances the cycle performance of the seawater hybrid rechargeable system, acting as a very stable interface layer between the Sn-C (Na storage) anode and the NASICON (Na3 Zr2 Si2 PO12) ceramic solid electrolyte, making this system extremely promising for cost-efficient and environmentally friendly large-scale energy storage.

47 patients with FLNA associated periventricular nodular heterotopia.

BACKGROUND: Heterozygous loss of function mutations within the Filamin A gene in Xq28 are the most frequent cause of bilateral neuronal periventricular nodular heterotopia (PVNH). Most affected females are reported to initially present with difficult to treat seizures at variable age of onset. Psychomotor development and cognition may be normal or mildly to moderately impaired. Distinct associated extracerebral findings have been observed and may help to establish the diagnosis including patent ductus arteriosus Botalli, progressive dystrophic cardiac valve disease and aortic dissection, chronic obstructive lung disease or chronic constipation. Genotype-phenotype correlations could not yet be established. METHODS: Sanger sequencing and MLPA was performed for a large cohort of 47 patients with Filamin A associated PVNH (age range 1 to 65 years). For 34 patients more detailed clinical information was available from a structured questionnaire and medical charts on family history, development, epileptologic findings, neurological examination, cognition and associated clinical findings. Available detailed cerebral MR imaging was assessed for 20 patients. RESULTS: Thirty-nine different FLNA mutations were observed, they are mainly truncating (37/39) and distributed throughout the entire coding region. No obvious correlation between the number and extend of PVNH and the severity of the individual clinical manifestation was observed. 10 of the mutation carriers so far are without seizures at a median age of 19.7 years. 22 of 24 patients with available educational data were able to attend regular school and obtain professional education according to age. CONCLUSIONS: We report the clinical and mutation spectrum as well as MR imaging for a large cohort of 47 patients with Filamin A associated PVNH including two adult males. Our data are reassuring in regard to psychomotor and cognitive development, which is within normal range for the majority of patients. However, a concerning median diagnostic latency of 17 to 20 years was noted between seizure onset and the genetic diagnosis, intensely delaying appropriate medical surveillance for potentially life threatening cardiovascular complications as well as genetic risk assessment and counseling prior to family planning for this X-linked dominant inherited disorder with high perinatal lethality in hemizygous males.