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Electrocatalysts are the cornerstone in the transition to sustainable energy technologies and chemical processes. Surface transformations under operation conditions dictate the activity and stability. However, the dependence of the surface structure and transformation on the exposed crystallographic facet remains elusive, impeding rational catalyst design. We investigate the (001), (110) and (111) facets of a LaNiO 3-δ electrocatalyst for water oxidation using electrochemical measurements, X-ray spectroscopy, and density functional theory calculations with a Hubbard U term. We reveal that the (111) overpotential is ≈ 30-60 mV lower than for the other facets. While a surface transformation into oxyhydroxide-like NiOO(H) may occur for all three orientations, it is more pronounced for (111). A structural mismatch of the transformed layer with the underlying perovskite for (001) and (110) influences the ratio of Ni 2+ and Ni 3+ to Ni 4+ sites during the reaction and thereby the binding energy of reaction intermediates, resulting in the distinct catalytic activities of the transformed facets., (© 2023. The Author(s).)

Background: Acute exposure to seizurogenic organophosphate (OP) nerve agents (OPNA) such as diisopropylfluorophosphate (DFP) or soman (GD), at high concentrations, induce immediate status epilepticus (SE), reactive gliosis, neurodegeneration, and epileptogenesis as a consequence. Medical countermeasures (MCMs-atropine, oximes, benzodiazepines), if administered in < 20 min of OPNA exposure, can control acute symptoms and mortality. However, MCMs alone are inadequate to prevent OPNA-induced brain injury and behavioral dysfunction in survivors. We have previously shown that OPNA exposure-induced SE increases the production of inducible nitric oxide synthase (iNOS) in glial cells in both short- and long- terms. Treating with a water soluble and highly selective iNOS inhibitor, 1400W, for 3 days significantly reduced OPNA-induced brain changes in those animals that had mild-moderate SE in the rat DFP model. However, such mitigating effects and the mechanisms of 1400W are unknown in a highly volatile nerve agent GD exposure., Methods: Mixed-sex cohort of adult Sprague Dawley rats were exposed to GD (132 μg/kg, s.c.) and immediately treated with atropine (2 mg/kg, i.m) and HI-6 (125 mg/kg, i.m.). Severity of seizures were quantified for an hour and treated with midazolam (3 mg/kg, i.m.). An hour post-midazolam, 1400W (20 mg/kg, i.m.) or vehicle was administered daily for 2 weeks. After behavioral testing and EEG acquisition, animals were euthanized at 3.5 months post-GD. Brains were processed for neuroinflammatory and neurodegeneration markers. Serum and CSF were used for nitrooxidative and proinflammatory cytokines assays., Results: We demonstrate a significant long-term (3.5 months post-soman) disease-modifying effect of 1400W in animals that had severe SE for > 20 min of continuous convulsive seizures. 1400W significantly reduced GD-induced motor and cognitive dysfunction; nitrooxidative stress (nitrite, ROS; increased GSH: GSSG); proinflammatory cytokines in the serum and some in the cerebrospinal fluid (CSF); epileptiform spikes and spontaneously recurring seizures (SRS) in males; reactive gliosis (GFAP + C3 and IBA1 + CD68-positive glia) as a measure of neuroinflammation, and neurodegeneration (especially parvalbumin-positive neurons) in some brain regions., Conclusion: These findings demonstrate the long-term disease-modifying effects of a glial-targeted iNOS inhibitor, 1400W, in a rat GD model by modulating reactive gliosis, neurodegeneration (parvalbumin-positive neurons), and neuronal hyperexcitability., (© 2023. The Author(s).)

The oxygen evolution reaction (OER) is one of the key kinetically limiting half reactions in electrochemical energy conversion. Model epitaxial catalysts have emerged as a platform to identify structure-function-relationships at the atomic level, a prerequisite to establish advanced catalyst design rules. Previous work identified an inverse relationship between activity and the stability of noble metal and oxide OER catalysts in both acidic and alkaline environments: The most active catalysts for the anodic OER are chemically unstable under reaction conditions leading to fast catalyst dissolution or amorphization, while the most stable catalysts lack sufficient activity. In this perspective, we discuss the role that epitaxial catalysts play in identifying this activity-stability-dilemma and introduce examples of how they can help overcome it. After a brief review of previously observed activity-stability-relationships, we will investigate the dependence of both activity and stability as a function of crystal facet. Our experiments reveal that the inverse relationship is not universal and does not hold for all perovskite oxides in the same manner. In fact, we find that facet-controlled epitaxial La 0.6 Sr 0.4 CoO 3-δ catalysts follow the inverse relationship, while for LaNiO 3-δ , the (111) facet is both the most active and the most stable. In addition, we show that both activity and stability can be enhanced simultaneously by moving from La-rich to Ni-rich termination layers. These examples show that the previously observed inverse activity-stability-relationship can be overcome for select materials and through careful control of the atomic arrangement at the solid-liquid interface. This realization re-opens the search for active and stable catalysts for water electrolysis that are made from earth-abundant elements. At the same time, these results showcase that additional stabilization via material design strategies will be required to induce a general departure from inverse stability-activity relationships among the transition metal oxide catalysts to ultimately grant access to the full range of available oxides for OER catalysis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wohlgemuth, Weber, Heymann, Baeumer and Gunkel.)

Epigenetic changes have been shown to be associated with both aging process and aging-related diseases. There is evidence regarding the benefits of physical activity on the functionality, cognition, and quality of life of institutionalized older adults, however, the molecular mechanisms involved are not elucidated. The purpose of this pilot study was to investigate the effects of a multimodal exercise intervention on functional outcomes, cognitive performance, quality of life (QOL), epigenetic markers and brain-derived neurotrophic factor (BDNF) levels among institutionalized older adult individuals. Participants (n = 8) without dementia who were aged 73.38 ± 11.28 years and predominantly female (87.5%) were included in this quasi-experimental pilot study. A multimodal exercise protocol (cardiovascular capacity, strength, balance/agility and flexibility, perception and cognition) consisted of twice weekly sessions (60 minutes each) over 8 weeks. Balance (Berg Scale), mobility (Timed Up and Go test), functional capacity (Six-Minute Walk test), cognitive function (Mini-Mental State Examination) and QOL (the World Health Organization Quality of Life-BREF Scale questionnaire) were evaluated before and after the intervention. Blood sample (15 mL) was also collected before and after intervention for analysis of biomarkers global histone H3 acetylation and brain-derived neurotrophic factor levels. Significant improvements were observed in cognitive function, balance, mobility, functional capacity and QOL after the intervention. In addition, a tendency toward an increase in global histone H3 acetylation levels was observed, while brain-derived neurotrophic factor level remained unchanged. This study provided evidence that an 8-week multimodal exercise protocol has a significant effect on ameliorating functional outcomes and QOL in institutionalized older adult individuals. In addition, it was also able to promote cognitive improvement, which seems to be partially related to histone hyperacetylation status. The Ethics Research Committee of Centro Universitário Metodista-IPA, Brazil approved the current study on June 6, 2019 (approval No. 3.376.078)., Competing Interests: None

1,4,5,8,9,11-hexaazatriphenylenehexacarbonitrile (HAT CN) was synthesized mechanochemically at room temperature. The coupling of hexaketocyclohexane and diaminomaleonitrile was conducted in 10 min by vibratory ball milling. The effects of milling parameters, acids, dehydrating agents, and liquid-assisted grinding were rationalized. With 67%, the yield of this mechanochemical approach exceeds that of state-of-the-art wet-chemical syntheses while being superior with respect to time-, resource-, and energy-efficiency as quantified via green metrics.

Landmark-guided navigation is a common behavioral strategy for way-finding, yet prior studies have not examined how animals collect sensory information to discriminate landmark features. We investigated this question in animals that rely on active sensing to guide navigation. Four echolocating bats ( Eptesicus fuscus ) were trained to use an acoustic landmark to find and navigate through a net opening for a food reward. In experimental trials, an object serving as a landmark was placed adjacent to a net opening and an object serving as a distractor was placed next to a barrier (covered opening). The location of the opening, barrier and objects were moved between trials, but the spatial relationships between the landmark and opening, and between the distractor and barrier were maintained. In probe trials, the landmark was placed next to a barrier, while the distractor was placed next to the opening, to test whether the bats relied on the landmark to guide navigation. Vocal and flight behaviors were recorded with an array of ultrasound microphones and high-speed infrared motion-capture cameras. All bats successfully learned to use the landmark to guide navigation through the net opening. Probe trials yielded an increase in both the time to complete the task and the number of net crashes, confirming that the bats relied largely on the landmark to find the net opening. Further, landmark acoustic distinctiveness influenced performance in probe trials and sonar inspection behaviors. Analyses of the animals' vocal behaviors also revealed differences between call features of bats inspecting landmarks compared with distractors, suggesting increased sonar attention to objects used to guide navigation., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

We introduce a general theoretical approach for the simulation of photochemical dynamics under the influence of circularly polarized light to explore the possibility of generating enantiomeric enrichment through polarized-light-selective photochemistry. The method is applied to the simulation of the photolysis of alanine, a prototype chiral amino acid. We show that a systematic enantiomeric enrichment can be obtained depending on the helicity of the circularly polarized light that induces the excited-state photochemistry of alanine. By analyzing the patterns of the photoinduced fragmentation of alanine we find an inducible enantiomeric enrichment up to 1.7%, which is also in good correspondence to the experimental findings. Our method is generally applicable to complex systems and might serve to systematically explore the photochemical origin of homochirality.

Facioscapulohumeral dystrophy (FSHD) is associated with somatic chromatin relaxation of the D4Z4 repeat array and derepression of the D4Z4-encoded DUX4 retrogene coding for a germline transcription factor. Somatic DUX4 derepression is caused either by a 1-10 unit repeat-array contraction (FSHD1) or by mutations in SMCHD1, which encodes a chromatin repressor that binds to D4Z4 (FSHD2). Here, we show that heterozygous mutations in DNA methyltransferase 3B (DNMT3B) are a likely cause of D4Z4 derepression associated with low levels of DUX4 expression from the D4Z4 repeat and increased penetrance of FSHD. Recessive mutations in DNMT3B were previously shown to cause immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome. This study suggests that transcription of DUX4 in somatic cells is modified by variations in its epigenetic state and provides a basis for understanding the reduced penetrance of FSHD within families., (Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

We present an efficient method for the simulation of time-resolved photoelectron imaging (TRPEI) spectra in polyatomic molecules. Our approach combines trajectory-based molecular dynamics that account for non-adiabatic effects using surface hopping, with an approximate treatment of the photoionization process using Dyson orbitals as initial and Coulomb waves as final electron states. The method has been implemented in the frame of linear response time-dependent density functional theory. As an illustration, we simulate time- and energy-resolved anisotropy maps for the furan molecule and compare them with recent experimental data [T. Fuji, Y.-I. Suzuki, T. Horio, T. Suzuki, R. Mitrić, U. Werner, and V. Bonačić-Koutecký, J. Chem. Phys. 133, 234303 (2010)]. Our method can be generally used for the interpretation of TRPEI experiments allowing to shed light into the fundamental photochemical processes in complex molecules.

We present a theoretical simulation of the ultrafast nonadiabatic photodynamics of tyrosine in the gas phase and in water. For this purpose, we combine our TDDFT/MM nonadiabatic dynamics (Wohlgemuth et al. J. Chem. Phys. 2011, 135, 054105) with the field-induced surface hopping method (Mitrić et al. Phys. Rev. A 2009, 79, 053416) allowing us to explicitly include the nonadiabatic effects as well as femtosecond laser excitation into the simulation. Our results reveal an ultrafast deactivation of the initially excited bright ππ* state by internal conversion to a dark nπ* state. We observe deactivation channels along the O-H stretching coordinate as well as involving the N-H bond cleavage of the amino group followed by proton transfer to the phenol ring, which is in agreement with previous static energy path calculations. However, since in the gas phase the canonical form of tyrosine is the most stable one, the proton transfer proceeds in two steps, starting from the carboxyl group that first passes its proton to the amino group, from where it finally moves to the phenol ring. Furthermore, we also investigate the influence of water on the relaxation processes. For the system of tyrosine with three explicit water molecules solvating the amino group, embedded in a classical water sphere, we also observe a relaxation channel involving proton transfer to the phenol ring. However, in aqueous environment, a water molecule near the protonated amino group of tyrosine acts as a mediator for the proton transfer, underlining the importance of the solvent in nonradiative relaxation processes of amino acids.

We present the extension of our field-induced surface hopping method for the description of the photoionization process and the simulation of time-resolved photoelectron spectra (TRPES). This is based on the combination of nonadiabatic molecular dynamics "on the fly" in the framework of TDDFT generalized for open shell systems under the influence of laser fields with the approximate quantum mechanical description of the photoionization process. Since arbitrary pulse shapes can be employed, this method can be also combined with the optimal control theory in order to steer the photoionization or to shape the outgoing electronic wavepackets. We illustrate our method for the simulation of TRPES on the prototype system of Ag(3), which involves excitation from the equilibrium triangular geometry, as well as excitation from the linear transition state, where in both cases nonadiabatic relaxation takes place in a complex manifold of electronic states. Our approach represents a generally applicable method for the prediction of time-resolved photoelectron spectra and their analysis in systems with complex electronic structure as well as many nuclear degrees freedom. This theoretical development should serve to stimulate new ultrafast experiments.

In this case-report we present a patient with a genetic disease which was first diagnosed in his eighties. The genetic disease is a rare neurologic disease, Kennedy's disease or spinobulbar muscular atrophy (SBMA). We also discuss the genetics of the disease and developments of future therapies.

A nonadiabatic molecular dynamics is implemented in the framework of the time-dependent density functional tight binding method (TDDFTB) combined with Tully's stochastic surface hopping algorithm. The applicability of our method to complex molecular systems is illustrated on the example of the ultrafast excited state dynamics of microsolvated adenine. Our results demonstrate that in the presence of water, upon initial excitation to the S(3) (pi-pi*) state at 260 nm, an ultrafast relaxation to the S(1) state with a time constant of 16 fs is induced, followed by the radiationless decay to the ground state with a time constant of 200 fs.

Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) is mainly characterized by progressive wasting and weakness of the facial, shoulder, and upper-arm muscles. FSHD is caused by contraction of the macrosatellite repeat D4Z4 on chromosome 4q35. The D4Z4 repeat is very polymorphic in length, and D4Z4 rearrangements occur almost exclusively via intrachromosomal gene conversions. Several disease mechanisms have been proposed, but none of these models can comprehensively explain FSHD, because repeat contraction alone is not sufficient to cause disease. Almost-identical D4Z4-repeat arrays have been identified on chromosome 10q26 and on two equally common chromosome 4 variants, 4qA and 4qB. Yet only repeat contractions of D4Z4 on chromosome 4qA cause FSHD; contractions on the other chromosomes are nonpathogenic. We hypothesized that allele-specific sequence differences among 4qA, 4qB, and 10q alleles underlie the 4qA specificity of FSHD. Sequence variations between these alleles have been described before, but the extent and significance of these variations proximal to, within, and distal to D4Z4 have not been studied in detail. We examined additional sequence variations in the FSHD locus, including a relatively stable simple sequence-length polymorphism proximal to D4Z4, a single-nucleotide polymorphism (SNP) within D4Z4, and the A/B variation distal to D4Z4. On the basis of these polymorphisms, we demonstrate that the subtelomeric domain of chromosome 4q can be subdivided into nine distinct haplotypes, of which three carry the distal 4qA variation. Interestingly, we show that repeat contractions in two of the nine haplotypes, one of which is a 4qA haplotype, are not associated with FSHD. We also show that each of these haplotypes has its unique sequence signature, and we propose that specific SNPs in the disease haplotype are essential for the development of FSHD.

Facioscapulohumeral muscular dystrophy (FSHD) is associated with contractions of the D4Z4 repeat in the subtelomere of chromosome 4q. Two allelic variants of chromosome 4q (4qA and 4qB) exist in the region distal to D4Z4. Although both variants are almost equally frequent in the population, FSHD is associated exclusively with the 4qA allele. We identified three families with FSHD in which each proband carries two FSHD-sized alleles and is heterozygous for the 4qA/4qB polymorphism. Segregation analysis demonstrated that FSHD-sized 4qB alleles are not associated with disease, since these were present in unaffected family members. Thus, in addition to a contraction of D4Z4, additional cis-acting elements on 4qA may be required for the development of FSHD. Alternatively, 4qB subtelomeres may contain elements that prevent FSHD pathogenesis.