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Background: Microglial activation is one hallmark of Alzheimer disease (AD) neuropathology but the impact of the regional interplay of microglia cells in the brain is poorly understood. We hypothesized that microglial activation is regionally synchronized in the healthy brain but experiences regional desynchronization with ongoing neurodegenerative disease. We addressed the existence of a microglia connectome and investigated microglial desynchronization as an AD biomarker., Methods: To validate the concept, we performed microglia depletion in mice to test whether interregional correlation coefficients (ICCs) of 18 kDa translocator protein (TSPO)-PET change when microglia are cleared. Next, we evaluated the influence of dysfunctional microglia and AD pathophysiology on TSPO-PET ICCs in the mouse brain, followed by translation to a human AD-continuum dataset. We correlated a personalized microglia desynchronization index with cognitive performance. Finally, we performed single-cell radiotracing (scRadiotracing) in mice to ensure the microglial source of the measured desynchronization., Results: Microglia-depleted mice showed a strong ICC reduction in all brain compartments, indicating microglia-specific desynchronization. AD mouse models demonstrated significant reductions of microglial synchronicity, associated with increasing variability of cellular radiotracer uptake in pathologically altered brain regions. Humans within the AD-continuum indicated a stage-depended reduction of microglia synchronicity associated with cognitive decline. scRadiotracing in mice showed that the increased TSPO signal was attributed to microglia., Conclusion: Using TSPO-PET imaging of mice with depleted microglia and scRadiotracing in an amyloid model, we provide first evidence that a microglia connectome can be assessed in the mouse brain. Microglia synchronicity is closely associated with cognitive decline in AD and could serve as an independent personalized biomarker for disease progression., (© 2024. The Author(s).)

Low-intensity noisy galvanic vestibular stimulation (nGVS) can improve static and dynamic postural deficits in patients with bilateral vestibular loss (BVL). In this study, we aimed to explore the neurophysiological and neuroanatomical substrates underlying nGVS treatment effects in a rat model of BVL. Regional brain activation patterns and behavioral responses to a repeated 30 min nGVS treatment in comparison to sham stimulation were investigated by serial whole-brain 18 F-FDG-PET measurements and quantitative locomotor assessments before and at nine consecutive time points up to 60 days after the chemical bilateral labyrinthectomy (BL). The 18 F-FDG-PET revealed a broad nGVS-induced modulation on regional brain activation patterns encompassing biologically plausible brain networks in the brainstem, cerebellum, multisensory cortex, and basal ganglia during the entire observation period post-BL. nGVS broadly reversed brain activity adaptions occurring in the natural course post-BL. The parallel behavioral locomotor assessment demonstrated a beneficial treatment effect of nGVS on sensory-ataxic gait alterations, particularly in the early stage of post-BL recovery. Stimulation-induced locomotor improvements were finally linked to nGVS brain activity responses in the brainstem, hemispheric motor, and limbic networks. In conclusion, combined 18 F-FDG-PET and locomotor analysis discloses the potential neurophysiological and neuroanatomical substrates that mediate previously observed therapeutic nGVS effects on postural deficits in patients with BVL.

Despite advances in therapeutics for heart failure and arrhythmias, a substantial proportion of patients with cardiomyopathy do not respond to interventions, indicating a need to identify novel modifiable myocardial pathobiology. Human genetic variation associated with severe forms of cardiomyopathy and arrhythmias has highlighted the crucial role of alternative splicing in myocardial health and disease, given that it determines which mature RNA transcripts drive the mechanical, structural, signalling and metabolic properties of the heart. In this Review, we discuss how the analysis of cardiac isoform expression has been facilitated by technical advances in multiomics and long-read and single-cell sequencing technologies. The resulting insights into the regulation of alternative splicing - including the identification of cardiac splice regulators as therapeutic targets and the development of a translational pipeline to evaluate splice modulators in human engineered heart tissue, animal models and clinical trials - provide a basis for improved diagnosis and therapy. Finally, we consider how the medical and scientific communities can benefit from facilitated acquisition and interpretation of splicing data towards improved clinical decision-making and patient care., (© 2023. Springer Nature Limited.)

Severe forms of dilated cardiomyopathy (DCM) are associated with point mutations in the alternative splicing regulator RBM20 that are frequently located in the arginine/serine-rich domain (RS-domain). Such mutations can cause defective splicing and cytoplasmic mislocalization, which leads to the formation of detrimental cytoplasmic granules. Successful development of personalized therapies requires identifying the direct mechanisms of pathogenic RBM20 variants. Here, we decipher the molecular mechanism of RBM20 mislocalization and its specific role in DCM pathogenesis. We demonstrate that mislocalized RBM20 RS-domain variants retain their splice regulatory activity, which reveals that aberrant cellular localization is the main driver of their pathological phenotype. A genome-wide CRISPR knockout screen combined with image-enabled cell sorting identified Transportin-3 (TNPO3) as the main nuclear importer of RBM20. We show that the direct RBM20-TNPO3 interaction involves the RS-domain, and is disrupted by pathogenic variants. Relocalization of pathogenic RBM20 variants to the nucleus restores alternative splicing and dissolves cytoplasmic granules in cell culture and animal models. These findings provide proof-of-principle for developing therapeutic strategies to restore RBM20's nuclear localization in RBM20-DCM patients., (© 2023. The Author(s).)

Dilated cardiomyopathy is the second most common cause for heart failure with no cure except a high-risk heart transplantation. Approximately 30% of patients harbor heritable mutations which are amenable to CRISPR-based gene therapy. However, challenges related to delivery of the editing complex and off-target concerns hamper the broad applicability of CRISPR agents in the heart. We employ a combination of the viral vector AAVMYO with superior targeting specificity of heart muscle tissue and CRISPR base editors to repair patient mutations in the cardiac splice factor Rbm20, which cause aggressive dilated cardiomyopathy. Using optimized conditions, we repair >70% of cardiomyocytes in two Rbm20 knock-in mouse models that we have generated to serve as an in vivo platform of our editing strategy. Treatment of juvenile mice restores the localization defect of RBM20 in 75% of cells and splicing of RBM20 targets including TTN. Three months after injection, cardiac dilation and ejection fraction reach wild-type levels. Single-nuclei RNA sequencing uncovers restoration of the transcriptional profile across all major cardiac cell types and whole-genome sequencing reveals no evidence for aberrant off-target editing. Our study highlights the potential of base editors combined with AAVMYO to achieve gene repair for treatment of hereditary cardiac diseases., (© 2023. The Author(s).)

Background: Recruiting study participants for clinical research is a challenging yet essential task. Social media platforms, such as Facebook, offer the opportunity to recruit participants through paid advertisements. These ad campaigns may be a cost-effective approach to reaching and recruiting participants who meet specific study criteria. However, little is known about the extent to which clicks on social media advertisements translate to the actual consent and enrollment of participants who meet the study criteria. Understanding this is especially important for clinical trials conducted remotely, such as telehealth-based studies, which open the possibility to recruit over large geographical areas and are becoming more common for the treatment of chronic health conditions, such as osteoarthritis (OA)., Objective: The aim of this study was to report on the conversion of clicks on a Facebook advertisement campaign to consent to enrollment in an ongoing telehealth physical therapy study for adults with knee OA, and the costs associated with recruitment., Methods: This was a secondary analysis using data collected over the first 5 months of an ongoing study of adults with knee OA. The Delaware Physical Exercise and Activity for Knee Osteoarthritis program compares a virtually delivered exercise program to a control group receiving web-based resources among adults with knee OA. Advertisement campaigns were configured on Facebook to reach an audience who could be potentially eligible. Clicking on the advertisement directed potential participants to a web-based screening form to answer 6 brief questions related to the study criteria. Next, a research team member called individuals who met the criteria from the screening form and verbally asked additional questions related to the study criteria. Once considered eligible, an electronic informed consent form (ICF) was sent. We described the number of potential study participants who made it through each of these steps and then calculated the cost per participant who signed the ICF., Results: In sum, between July and November 2021, a total of 33,319 unique users saw at least one advertisement, 9879 clicks were made, 423 web-based screening forms were completed, 132 participants were successfully contacted, 70 were considered eligible, and 32 signed the ICF. Recruitment costed an average of US $51.94 per participant., Conclusions: While there was a low conversion from clicks to actual consent, 32% (32/100) of the total sample required for the study were expeditiously consented over 5 months with a per-subject cost well below traditional means of recruitment, which ranges from US $90 to US $1000 per participant., Trial Registration: Clinicaltrails.gov NCT04980300; https://clinicaltrials.gov/ct2/show/NCT04980300., (©Jéssica Bianca Aily, Jennifer Copson, Dana Voinier, Jason Jakiela, Rana Hinman, Megan Grosch, Colleen Noonan, Megan Armellini, Laura Schmitt, Mika White, Daniel White. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 18.05.2023.)

The Fischer-Tropsch (FT) process converts a mixture of CO and H 2 into liquid hydrocarbons as a major component of the gas-to-liquid technology for the production of synthetic fuels. Contrary to the energy-demanding chemical FT process, the enzymatic FT-type reactions catalyzed by nitrogenase enzymes, their metalloclusters, and synthetic mimics utilize H + and e - as the reducing equivalents to reduce CO, CO 2 , and CN - into hydrocarbons under ambient conditions. The C 1 chemistry exemplified by these FT-type reactions is underscored by the structural and electronic properties of the nitrogenase-associated metallocenters, and recent studies have pointed to the potential relevance of this reactivity to nitrogenase mechanism, prebiotic chemistry, and biotechnological applications. This review will provide an overview of the features of nitrogenase enzymes and associated metalloclusters, followed by a detailed discussion of the activities of various nitrogenase-derived FT systems and plausible mechanisms of the enzymatic FT reactions, highlighting the versatility of this unique reactivity while providing perspectives onto its mechanistic, evolutionary, and biotechnological implications.

Aim: We aimed to investigate the impact of microglial activity and microglial FDG uptake on metabolic connectivity, since microglial activation states determine FDG-PET alterations. Metabolic connectivity refers to a concept of interacting metabolic brain regions and receives growing interest in approaching complex cerebral metabolic networks in neurodegenerative diseases. However, underlying sources of metabolic connectivity remain to be elucidated., Materials and Methods: We analyzed metabolic networks measured by interregional correlation coefficients (ICCs) of FDG-PET scans in WT mice and in mice with mutations in progranulin (Grn) or triggering receptor expressed on myeloid cells 2 (Trem2) knockouts ( -/- ) as well as in double mutant Grn -/- /Trem2 -/- mice. We selected those rodent models as they represent opposite microglial signatures with disease associated microglia in Grn -/- mice and microglia locked in a homeostatic state in Trem2 -/- mice; however, both resulting in lower glucose uptake of the brain. The direct influence of microglia on metabolic networks was further determined by microglia depletion using a CSF1R inhibitor in WT mice at two different ages. Within maps of global mean scaled regional FDG uptake, 24 pre-established volumes of interest were applied and assigned to either cortical or subcortical networks. ICCs of all region pairs were calculated and z-transformed prior to group comparisons. FDG uptake of neurons, microglia, and astrocytes was determined in Grn -/- and WT mice via assessment of single cell tracer uptake (scRadiotracing)., Results: Microglia depletion by CSF1R inhibition resulted in a strong decrease of metabolic connectivity defined by decrease of mean cortical ICCs in WT mice at both ages studied (6-7 m; p = 0.0148, 9-10 m; p = 0.0191), when compared to vehicle-treated age-matched WT mice. Grn -/- , Trem2 -/- and Grn -/- /Trem2 -/- mice all displayed reduced FDG-PET signals when compared to WT mice. However, when analyzing metabolic networks, a distinct increase of ICCs was observed in Grn -/- mice when compared to WT mice in cortical (p < 0.0001) and hippocampal (p < 0.0001) networks. In contrast, Trem2 -/- mice did not show significant alterations in metabolic connectivity when compared to WT. Furthermore, the increased metabolic connectivity in Grn -/- mice was completely suppressed in Grn -/- /Trem2 -/- mice. Grn -/- mice exhibited a severe loss of neuronal FDG uptake (- 61%, p < 0.0001) which shifted allocation of cellular brain FDG uptake to microglia (42% in Grn -/- vs. 22% in WT)., Conclusions: Presence, absence, and activation of microglia have a strong impact on metabolic connectivity of the mouse brain. Enhanced metabolic connectivity is associated with increased microglial FDG allocation., (© 2023. The Author(s).)

RBM20 cardiomyopathy is an arrhythmogenic form of dilated cardiomyopathy caused by mutations in the splicing factor RBM20. A recent study found a more severe phenotype in male patients with RBM20 cardiomyopathy patients than in female patients. Here, we aim to determine sex differences in an animal model of RBM20 cardiomyopathy and investigate potential underlying mechanisms. In addition, we aim to determine sex and gender differences in clinical parameters in a novel RBM20 cardiomyopathy patient cohort. We characterized an Rbm20 knockout (KO) mouse model, and show that splicing of key RBM20 targets, cardiac function, and arrhythmia susceptibility do not differ between sexes. Next, we performed deep phenotyping of these mice, and show that male and female Rbm20 -KO mice possess transcriptomic and phosphoproteomic differences. Hypothesizing that these differences may influence the heart's ability to compensate for stress, we exposed Rbm20 -KO mice to acute catecholaminergic stimulation and again found no functional differences. We also replicate the lack of functional differences in a mouse model with the Rbm20 -R636Q mutation. Lastly, we present a patient cohort of 33 RBM20 cardiomyopathy patients and show that these patients do not possess sex and gender differences in disease severity. Current mouse models of RBM20 cardiomyopathy show more pronounced changes in gene expression and phosphorylation of cardiac proteins in male mice, but no sex differences in cardiac morphology and function. Moreover, other than reported before, male RBM20 cardiomyopathy patients do not present with worse cardiac function in a patient cohort from Germany and the Netherlands. NEW & NOTEWORTHY Optimal management of the cardiac disease is increasingly personalized, partly because of differences in outcomes between sexes. RBM20 cardiomyopathy has been described to be more severe in male patients, and this carries the risk that male patients are more scrutinized in the clinic than female patients. Our findings do not support this observation and suggest that treatment should not differ between male and female RBM20 cardiomyopathy patients, but instead should focus on the underlying disease mechanism.

Despite their fundamental role in assessing (patho)physiological cell states, conventional gene reporters can follow gene expression but leave scars on the proteins or substantially alter the mature messenger RNA. Multi-time-point measurements of non-coding RNAs are currently impossible without modifying their nucleotide sequence, which can alter their native function, half-life and localization. Thus, we developed the intron-encoded scarless programmable extranuclear cistronic transcript (INSPECT) as a minimally invasive transcriptional reporter embedded within an intron of a gene of interest. Post-transcriptional excision of INSPECT results in the mature endogenous RNA without sequence alterations and an additional engineered transcript that leaves the nucleus by hijacking the nuclear export machinery for subsequent translation into a reporter or effector protein. We showcase its use in monitoring interleukin-2 (IL2) after T cell activation and tracking the transcriptional dynamics of the long non-coding RNA (lncRNA) NEAT1 during CRISPR interference-mediated perturbation. INSPECT is a method for monitoring gene transcription without altering the mature lncRNA or messenger RNA of the target of interest., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The Fe protein of nitrogenase plays multiple roles in substrate reduction and metallocluster assembly. Best known for its function to transfer electrons to its catalytic partner during nitrogenase catalysis, the Fe protein is also a key player in the biosynthesis of the complex metalloclusters of nitrogenase. In addition, it can function as a reductase on its own and affect the ambient reduction of CO 2 or CO to hydrocarbons. This review will provide an overview of the properties and functions of the Fe protein, highlighting the relevance of this unique FeS enzyme to areas related to the catalysis, biosynthesis, and applications of the fascinating nitrogenase system.

The promise of hybrid organic-inorganic halide perovskite solar cells rests on their exceptional power conversion efficiency routinely exceeding 25% in laboratory scale devices. While the migration of halide ions in perovskite thin films has been extensively investigated, the understanding of cation diffusion remains elusive. In this study, a thermal migration of A‑site cations at the solid-solid interface, formed by two physically paired MAPbI 3 and FAPbI 3 perovskite thin films casted on FTO, is demonstrated through continuous annealing at comparably low temperature (100 °C). Diffusion of methylammonium (CH 3 NH 3 + , MA + ) cations into the low‑symmetry yellow δ‑FAPbI 3 phase triggers a transition from the yellow (δ) to black (α) phase evident in the distinctive color change and verified by shifts in absorption bands and X‑ray diffraction patterns. Intermixing of the A‑site cations MA + and FA + (CH(NH 2 ) 2 + ) occurred for both systems, α‑MAPbI 3 /δ‑FAPbI 3 and α‑MAPbI 3 /α‑FAPbI 3 . The structural and compositional changes in both cases support a thermally activated ion drift unambiguously demonstrated through changes in the absorption and X-ray photoelectron spectra. Moreover, the physical contact annealing (PCA) leads to healing of defects and pinholes in α‑MAPbI 3 thin films, which was correlated to longer recombination lifetimes in mixed MA x FA 1-x PbI 3 thin films obtained after PCA and probed by ultrafast transient absorption spectroscopy., (© 2022. The Author(s).)

An acute unilateral vestibulopathy leads to symptoms of vestibular tone imbalance, which gradually decrease over days to weeks due to central vestibular compensation. Animal models of acute peripheral vestibular lesions are optimally suited to investigate the mechanisms underlying this lesion-induced adaptive neuroplasticity. Previous studies applied ex vivo histochemical techniques or local in vivo electrophysiological recordings mostly in the vestibular nucleus complex to delineate the mechanisms involved. Recently, the use of imaging methods, such as positron emission tomography (PET) or magnetic resonance imaging (MRI), in vestibular animal models have opened a complementary perspective by depicting whole-brain structure and network changes of neuronal activity over time and in correlation to behaviour. Here, we review recent multimodal imaging studies in vestibular animal models with a focus on PET-based measurements of glucose metabolism, glial activation and synaptic plasticity. [18F]-FDG-PET studies indicate dynamic alterations of regional glucose metabolism in brainstem-cerebellar, thalamic, cortical sensory and motor, as well as limbic areas starting early after unilateral labyrinthectomy (UL) in the rat. Sequential whole-brain analysis of the metabolic connectome during vestibular compensation shows a significant increase of connections mostly in the contralesional hemisphere after UL, which reaches a maximum at day 3 and thereby parallels the course of vestibular recovery. Glial activation in the ipsilesional vestibular nerve and nucleus peak between days 7 and 15 after UL. Synaptic density in brainstem-cerebellar circuits decreases until 8 weeks after UL, while it increases in frontal, motor and sensory cortical areas. We finally report how pharmacological compounds modulate the functional and structural plasticity mechanisms during vestibular compensation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Neuronal lesions trigger mechanisms of structural and functional neuroplasticity, which can support recovery. However, the temporal and spatial appearance of structure-function changes and their interrelation remain unclear. The current study aimed to directly compare serial whole-brain in vivo measurements of functional plasticity (by [ 18 F]FDG-PET) and structural synaptic plasticity (by [ 18 F]UCB-H-PET) before and after bilateral labyrinthectomy in rats and investigate the effect of locomotor training. Complex structure-function changes were found after bilateral labyrinthectomy: in brainstem-cerebellar circuits, regional cerebral glucose metabolism (rCGM) decreased early, followed by reduced synaptic density. In the thalamus, increased [ 18 F]UCB-H binding preceded a higher rCGM uptake. In frontal-basal ganglia loops, an increase in synaptic density was paralleled by a decrease in rCGM. In the group with locomotor training, thalamic rCGM and [ 18 F]UCB-H binding increased following bilateral labyrinthectomy compared to the no training group. Rats with training had considerably fewer body rotations. In conclusion, combined [ 18 F]FDG/[ 18 F]UCB-H dual tracer imaging reveals that adaptive neuroplasticity after bilateral vestibular loss is not a uniform process but is composed of complex spatial and temporal patterns of structure-function coupling in networks for vestibular, multisensory, and motor control, which can be modulated by early physical training., (© 2022. The Author(s).)

Sulfur-assisted corrosion is a process known to material scientists for many decades now. Though the corrosion of iron in the presence of sulfur has been studied extensively, it has never been used to intentionally synthesize mackinawite. In contrast to the conventional preparation of mackinawite by precipitation, the synthesis from the elements can be carried out without additional ions. This makes it possible to investigate the influence of any dissolved salts on the mackinawite formation and its properties. We found that the addition of NaCl significantly accelerates the reaction and furthermore influences the Fe 2+ ion content of the formed mackinawite itself. This finding leads us to propose a novel model of charged layers which can be used to explain some of the inconsistencies found in the literature regarding the structure and particle characteristics of nano-mackinawite., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The interest in transition metal dichalcogenides (TMDCs; ME y/2 ; M = transition metal; E = chalcogenide, y = valence of the metal) has grown exponentially across various science and engineering disciplines due to their unique structural chemistry manifested in a two-dimensional lattice that results in extraordinary electronic and transport properties desired for applications in sensors, energy storage and optoelectronic devices. Since the properties of TMDCs can be tailored by changing the stacking sequence of 2D monolayers with similar or dis-similar materials, a number of synthetic routes essentially based on the disintegration of bulk ( e.g. , chemical exfoliation) or the integration of atomic constituents ( e.g. , vapor phase growth) have been explored. Despite a large body of data available on the chemical synthesis of TMDCs, experimental strategies with high repeatability of control over film thickness, phase and compositional purity remain elusive, which calls for innovative synthetic concepts offering, for instance, self-limited growth in the z -direction and homogeneous lateral topography. This review summarizes the recent conceptual advancements in the growth of layered van der Waals TMDCs from both mixtures of metal and chalcogen sources (multi-source precursors; MSPs) and from molecular compounds containing metals and chalcogens in one starting material (single-source precursor; SSPs). The critical evaluation of the strengths, limitations and opportunities of MSP and SSP approaches is provided as a guideline for the fabrication of TMDCs from commercial and customized molecular precursors. For example, alternative synthetic pathways using tailored molecular precursors circumvent the challenges of differential nucleation and crystal growth kinetics that are invariably associated with conventional gas phase chemical vapor transport (CVT) and chemical vapor deposition (CVD) of a mixture of components. The aspects of achieving high compositional purity and alternatives to minimize competing reactions or side products are discussed in the context of efficient chemical synthesis of TMDCs. Moreover, a critical analysis of the potential opportunities and existing bottlenecks in the synthesis of TMDCs and their intrinsic properties is provided.

The catalytic conversion of nitrogen to ammonia remains an energy-intensive process, demanding advanced concepts for nitrogen fixation. The major obstacle of nitrogen fixation lies in the intrinsically high bond energy (941 kJ mol -1 ) of the N≡N molecule and the absence of a permanent dipole in N 2 . This kinetic barrier is addressed in this study by an efficient piezo-enhanced gold catalysis as demonstrated by the room temperature reduction of dinitrogen into ammonia. Au nanostructures were immobilized on thin film piezoelectric support of potassium sodium niobate (K 0.5 Na 0.5 NbO 3 , KNN) by chemical vapor deposition of a new Au(III) precursor [Me 2 Au(PyTFP)(H 2 O)] 1 (PyTFP = ( Z )-3,3,3-trifluoro-1-(pyridin-2-yl)-prop-1-en-2-olate) that exhibited high volatility (60 °C, 10 -3 mbar) and clean decomposition mechanism to produce well adherent elemental gold films on KNN and Ti substrates. The gold-functionalized KNN films served as an efficient catalytic system for ammonia production with a Faradaic efficiency of 18.9% achieved upon ultrasonic actuation. Our results show that the spontaneous polarization of piezoelectric materials under external electrical fields augments the sluggish electron transfer kinetics by creating instant dipoles in adsorbed N 2 molecules to deliver a piezo-enhanced catalytic system promising for sustained activation of dinitrogen molecules., (© 2021 IOP Publishing Ltd.)

Mutations in the PKD2 gene cause autosomal-dominant polycystic kidney disease but the physiological role of polycystin-2, the protein product of PKD2, remains elusive. Polycystin-2 belongs to the transient receptor potential (TRP) family of non-selective cation channels. To test the hypothesis that altered ion channel properties of polycystin-2 compromise its putative role in a control circuit controlling lumen formation of renal tubular structures, we generated a mouse model in which we exchanged the pore loop of polycystin-2 with that of the closely related cation channel polycystin-2L1 (encoded by PKD2L1), thereby creating the protein polycystin-2poreL1. Functional characterization of this mutant channel in Xenopus laevis oocytes demonstrated that its electrophysiological properties differed from those of polycystin-2 and instead resembled the properties of polycystin-2L1, in particular regarding its permeability for Ca2+ ions. Homology modeling of the ion translocation pathway of polycystin-2poreL1 argues for a wider pore in polycystin-2poreL1 than in polycystin-2. In Pkd2poreL1 knock-in mice in which the endogenous polycystin-2 protein was replaced by polycystin-2poreL1 the diameter of collecting ducts was increased and collecting duct cysts developed in a strain-dependent fashion., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Metabolic connectivity patterns on the basis of [ 18 F]-FDG positron emission tomography (PET) are used to depict complex cerebral network alterations in different neurological disorders and therefore may have the potential to support diagnostic decisions. In this study, we established a novel statistical classification method taking advantage of differential time-dependent states of whole-brain metabolic connectivity following unilateral labyrinthectomy (UL) in the rat and explored its classification accuracy. The dataset consisted of repeated [ 18 F]-FDG PET measurements at baseline and 1, 3, 7, and 15 days (= maximum of 5 classes) after UL with 17 rats per measurement day. Classification in different stages after UL was performed by determining connectivity patterns for the different classes by Pearson's correlation between uptake values in atlas-based segmented brain regions. Connections were fitted with a linear function, with which different thresholds on the correlation coefficient (r = [0.5, 0.85]) were investigated. Rats were classified by determining the congruence of their PET uptake pattern with the fitted connectivity patterns in the classes. Overall, the classification accuracy with this method was 84.3% for 3 classes, 75.0% for 4 classes, and 54.1% for 5 classes and outperformed random classification as well as machine learning classification on the same dataset. The optimal classification thresholds of the correlation coefficient and distance-to-fit were found to be |r| > 0.65 and d = 4 when using Siegel's slope estimator for fitting. This connectivity-based classification method can compete with machine learning classification and may have methodological advantages when applied to support PET-based diagnostic decisions in neurological network disorders (such as neurodegenerative syndromes)., (Copyright © 2021. Published by Elsevier Inc.)

Unilateral damage to the inner ear results in an acute vestibular syndrome, which is compensated within days to weeks due to adaptive cerebral plasticity. This process, called central vestibular compensation (VC), involves a wide range of functional and structural mechanisms at the cellular and network level. The short-term dynamics of whole-brain functional network recruitment and recalibration during VC has not been depicted in vivo. The purpose of this study was to investigate the interplay of separate and distinct brain regions and in vivo networks in the course of VC by sequential [ 18 F]-FDG-PET-based statistical and graph theoretical analysis with the aim of revealing the metabolic connectome before and 1, 3, 7, and 15 days post unilateral labyrinthectomy (UL) in the rat. Temporal changes in metabolic brain connectivity were determined by Pearson's correlation (|r| > 0.5, p < 0.001) of regional cerebral glucose metabolism (rCGM) in 57 segmented brain regions. Metabolic connectivity analysis was compared to univariate voxel-wise statistical analysis of rCGM over time and to behavioral scores of static and dynamic sensorimotor recovery. Univariate statistical analysis revealed an ipsilesional relative rCGM decrease (compared to baseline) and a contralesional rCGM increase in vestibular and limbic networks and an increase in bilateral cerebellar and sensorimotor networks. Quantitative analysis of the metabolic connections showed a maximal increase from baseline to day 3 post UL (interhemispheric: 2-fold, ipsilesional: 3-fold, contralesional: 12-fold) and a gradual decline until day 15 post UL, which paralleled the dynamics of vestibular symptoms. In graph theoretical analysis, an increase in connectivity occurred especially within brain regions associated with brainstem-cerebellar and thalamocortical vestibular networks and cortical sensorimotor networks. At the symptom peak (day 3 post UL), brain networks were found to be organized in large ensembles of distinct and highly connected hubs of brain regions, which separated again with progressing VC. Thus, we found rapid changes in network organization at the subcortical and cortical level and in both hemispheres, which may indicate an initial functional substitution of vestibular loss and subsequent recalibration and reorganization of sensorimotor networks during VC., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Chemical vapor deposition (CVD) of UO 2 thin films from in situ reductive decomposition using a U(VI) precursor ([U(O t Bu) 6 ]) was performed under applied magnetic fields (up to 1 T). The molecular mechanism responsible for the formation of U(IV) oxide was determined by nuclear magnetic resonance (NMR) analysis of gaseous byproducts revealed a reductive transformation of uranium hexakis - tert -butoxide into urania. Thin films were grown under zero-field and applied magnetic field conditions that clearly showed the guiding influence of the magnetic field on altering the morphology and crystallographic orientation of grains in UO 2 deposits produced under an external magnetic field. Application of magnetic fields was found to reduce the grain size. Whereas films with a ⟨111⟩ preferred orientation were observed under zero-field conditions, the application of magnetic fields (500 mT to 1 T) promoted a polycrystalline growth. X-ray photoelectron spectroscopy confirmed the formation of UO 2 films with traces of U(VI) centers present on the surface, which was evidently due to the surface oxidation of coordinatively unsaturated U(IV) centers, which was found to be significantly reduced in the field-assisted process. These findings emphasize the positive effect of magnetic fields on controlling the texture and chemical homogeneity of CVD-grown films. The availability of a magnetic field as an extrinsic parameter for the CVD process adds to the conventional parameters, such as temperature, deposition time, and pressure, and expands the experimental space for thin-film growth.