Tailored re-roofing technique for pulsatile tinnitus caused by sigmoid sinus dehiscence or diverticulum.

Background: Sigmoid sinus diverticulum/dehiscence (SSD) is one of the treatable causes of venous pulsatile tinnitus. It can be diagnosed using temporal bone computed tomography (CT) or magnetic resonance angiography/venography (MRA). In cases where patients find their symptoms intolerable, surgical treatment is typically preferred. Here, we have presented a novel surgical technique involving sigmoid sinus re-roofing and have analyzed its feasibility. Methods: Between January 2020 and July 2023, approximately 150 patients with pulsatile tinnitus were evaluated at two different tertiary hospitals. Of these, 12 patients were diagnosed with SSD, and seven underwent surgical treatment. Five patients were treated with tailored reroofing (TRR) of the sigmoid sinus and two with transmastoid resurfacing (MRS) of the sigmoid sinus. We compared the Korean tinnitus handicap inventory (K-THI) score, pure tone audiogram (PTA) threshold, and CT findings before and a month after surgeries for these two techniques. The operation time was also analyzed. Results: In TRR cases, the K-THI score reduced from 55.0 ± 31.4 preoperatively to 4.0 ± 3.0 postoperatively, and the SSD was well-repositioned and covered by a bone chip postoperatively. In MRS cases, the K-THI score reduced from 41.0 ± 9.9 preoperatively to 15.0 ± 21.2 postoperatively, and the SSD was well-covered with bone cement postoperatively. The average surgical time of five TRR and two MRS cases were 77.5 ± 32.5 and 174.0 ± 75.0 min, respectively. No complications were noted. Conclusions: Despite the insufficient number of cases, we noted that TRR requires a reasonable amount of time, involves a smaller incision, and may provide favorable outcomes compared to conventional MRS in cases of pulsatile tinnitus associated with SSD. Level of evidence: IV.

Structure Effects of Ligands in Gold-Ligand Complexes for Controlled Formation of Gold Nanoclusters.

Metal nanoclusters (NCs) are a special class of nanoparticles composed of a precise number of metal atoms and ligands. Because the proportion of ligands to metal atoms is high in metal NCs, the ligand type determines the physical properties of metal NCs. Furthermore, ligands presumably govern the entire formation process of the metal NCs. However, their roles in the synthesis, especially as factors in the uniformity of metal NCs, are not understood. It is because the synthetic procedure of metal NCs is highly convoluted. The synthesis is initiated by the formation of various metal-ligand complexes, which have different numbers of atoms and ligands, resulting in different coordinations of metal. Moreover, these complexes, as actual precursors to metal NCs, undergo sequential transformations into a series of intermediate NCs before the formation of the desired NCs. Thus, to resolve the complicated synthesis of metal NCs and achieve their uniformity, it is important to investigate the reactivity of the complexes. Herein, we utilize a combination of mass spectrometry, density functional theory, and electrochemical measurements to understand the ligand effects on the reactivity of AuI-thiolate complexes toward the reductive formation of Au NCs. We discover that the stability of the complexes can be increased by either van der Waals interactions induced by the long carbon chain of ligands or by non-thiol functional groups in the ligands, which additionally coordinate with AuI in the complexes. Such structural effects of thiol ligands determine the reduction reactivity of the complexes and the amount of NaBH4 required for the controlled synthesis of the Au NCs.

Posttranscriptional regulation of FAN1 by miR-124-3p at rs3512 underlies onset-delaying genetic modification in Huntington's disease.

Many Mendelian disorders, such as Huntington's disease (HD) and spinocerebellar ataxias, arise from expansions of CAG trinucleotide repeats. Despite the clear genetic causes, additional genetic factors may influence the rate of those monogenic disorders. Notably, genome-wide association studies discovered somewhat expected modifiers, particularly mismatch repair genes involved in the CAG repeat instability, impacting age at onset of HD. Strikingly, FAN1, previously unrelated to repeat instability, produced the strongest HD modification signals. Diverse FAN1 haplotypes independently modify HD, with rare genetic variants diminishing DNA binding or nuclease activity of the FAN1 protein, hastening HD onset. However, the mechanism behind the frequent and the most significant onset-delaying FAN1 haplotype lacking missense variations has remained elusive. Here, we illustrated that a microRNA acting on 3'-UTR (untranslated region) SNP rs3512, rather than transcriptional regulation, is responsible for the significant FAN1 expression quantitative trait loci signal and allelic imbalance in FAN1 messenger ribonucleic acid (mRNA), accounting for the most significant and frequent onset-delaying modifier haplotype in HD. Specifically, miR-124-3p selectively targets the reference allele at rs3512, diminishing the stability of FAN1 mRNA harboring that allele and consequently reducing its levels. Subsequent validation analyses, including the use of antagomir and 3'-UTR reporter vectors with swapped alleles, confirmed the specificity of miR-124-3p at rs3512. Together, these findings indicate that the alternative allele at rs3512 renders the FAN1 mRNA less susceptible to miR-124-3p-mediated posttranscriptional regulation, resulting in increased FAN1 levels and a subsequent delay in HD onset by mitigating CAG repeat instability.

A Systemic Immune Inflammation Index and PD-L1 (SP142) Expression as a Potential Combined Biomarker of the Clinical Benefit of Chemo-Immunotherapy in Extensive-Stage Small-Cell Lung Cancer.

Background: No studies have identified combined biomarkers that may be more reasonable for the assessment of current chemo-immunotherapy in patients with extensive stage small-cell lung cancer (ES-SCLC). Methods: This study was conducted to investigate a combined biomarker with prognostic or predictive value in ES-SCLC. We determined the best independent prognostic biomarker among the four complete blood-count-derived inflammatory biomarkers (CBC-IBs). Subsequently, we analyzed the prognostic or predictive value of combining this independent CBC-IB with PD-L1 (SP142) expression. We prospectively assessed the SP142 analyses in tumor samples at diagnosis. Results: All in all, 55 patients with ES-SCLC were classified into four groups according to the systemic immune inflammation index (SII) (low/high) and SP142 (positive/negative). The best survival was observed in the low-SII/ SP142-positive group, whereas the worst survival was observed in the high-SII/SP142-negative group (p = 0.002). The combined SII-SP142 biomarker was better for predicting both survival and disease progression in patients with ES-SCLC. Conclusions: The combined SII-SP142 biomarker can be readily and universally obtained at a low cost in clinical practice, without requiring advanced genomics technology or specialized expertise. Although further studies are needed to confirm that the combined SII-SP142 biomarker is widely applicable, it should help clinicians to identify the best patients for combined chemotherapy with atezolizumab in ES-SCLC.

Modification of Huntington's disease by short tandem repeats.

Expansions of glutamine-coding CAG trinucleotide repeats cause a number of neurodegenerative diseases, including Huntington's disease and several of spinocerebellar ataxias. In general, age-at-onset of the polyglutamine diseases is inversely correlated with the size of the respective inherited expanded CAG repeat. Expanded CAG repeats are also somatically unstable in certain tissues, and age-at-onset of Huntington's disease corrected for individual HTT CAG repeat length (i.e. residual age-at-onset), is modified by repeat instability-related DNA maintenance/repair genes as demonstrated by recent genome-wide association studies. Modification of one polyglutamine disease (e.g. Huntington's disease) by the repeat length of another (e.g. ATXN3, CAG expansions in which cause spinocerebellar ataxia 3) has also been hypothesized. Consequently, we determined whether age-at-onset in Huntington's disease is modified by the CAG repeats of other polyglutamine disease genes. We found that the CAG measured repeat sizes of other polyglutamine disease genes that were polymorphic in Huntington's disease participants but did not influence Huntington's disease age-at-onset. Additional analysis focusing specifically on ATXN3 in a larger sample set (n = 1388) confirmed the lack of association between Huntington's disease residual age-at-onset and ATXN3 CAG repeat length. Additionally, neither our Huntington's disease onset modifier genome-wide association studies single nucleotide polymorphism data nor imputed short tandem repeat data supported the involvement of other polyglutamine disease genes in modifying Huntington's disease. By contrast, our genome-wide association studies based on imputed short tandem repeats revealed significant modification signals for other genomic regions. Together, our short tandem repeat genome-wide association studies show that modification of Huntington's disease is associated with short tandem repeats that do not involve other polyglutamine disease-causing genes, refining the landscape of Huntington's disease modification and highlighting the importance of rigorous data analysis, especially in genetic studies testing candidate modifiers.

Probing Local pH Change during Electrode Oxidation of TEMPO Derivative: Implication of Redox-Induced Acidity Alternation by Imidazolium-Linker Functional Groups.

The chemical degradation of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-based aqueous energy storage and catalytic systems is pH sensitive. Herein, we voltammetrically monitor the local pH (pHlocal) at a Pt ultramicroelectrode (UME) upon electro-oxidation of imidazolium-linker functionalized TEMPO and show that its decrease is associated with the greater acidity of the cationic (oxidized) rather than radical (reduced) form of TEMPO. The protons that drive the decrease in pH arise from hydrolysis of the conjugated imidazolium-linker functional group of 4-[2-(N-methylimidazolium)acetoxy]-2,2,6,6-tetramethylpiperidine-1-oxyl chloride (MIMAcO-T), which was studied in comparison with 4-hydroxyl-TEMPO (4-OH-T). Voltammetric hysteresis is observed during the electrode oxidation of 4-OH-T and MIMAcO-T at a Pt UME in an unbuffered aqueous solution. The hysteresis arises from the pH-dependent formation and dissolution of Pt oxides, which interact with pHlocal in the vicinity of the UME. We find that electrogenerated MIMAcO-T+ significantly influences pHlocal, whereas 4-OH-T+ does not. Finite element analysis reveals that the thermodynamic and kinetic acid-base properties of MIMAcO-T+ are much more favorable than those of its reduced counterpart. Imidazolium-linker functionalized TEMPO molecules comprising different linking groups were also investigated. Reduced TEMPO molecules with carbonyl linkers behave as weak acids, whereas those with alkyl ether linkers do not. However, oxidized TEMPO+ molecules with alkyl ether linkers exhibit more facile acid-base kinetics than those with carbonyl ones. Density functional theory calculations confirm that OH- adduct formation on the imidazolium-linker functional group of TEMPO is responsible for the difference in the acid-base properties of the reduced and oxidized forms.

Area-selective atomic layer deposition on 2D monolayer lateral superlattices.

The advanced patterning process is the basis of integration technology to realize the development of next-generation high-speed, low-power consumption devices. Recently, area-selective atomic layer deposition (AS-ALD), which allows the direct deposition of target materials on the desired area using a deposition barrier, has emerged as an alternative patterning process. However, the AS-ALD process remains challenging to use for the improvement of patterning resolution and selectivity. In this study, we report a superlattice-based AS-ALD (SAS-ALD) process using a two-dimensional (2D) MoS2-MoSe2 lateral superlattice as a pre-defining template. We achieved a minimum half pitch size of a sub-10 nm scale for the resulting AS-ALD on the 2D superlattice template by controlling the duration time of chemical vapor deposition (CVD) precursors. SAS-ALD introduces a mechanism that enables selectivity through the adsorption and diffusion processes of ALD precursors, distinctly different from conventional AS-ALD method. This technique facilitates selective deposition even on small pattern sizes and is compatible with the use of highly reactive precursors like trimethyl aluminum. Moreover, it allows for the selective deposition of a variety of materials, including Al2O3, HfO2, Ru, Te, and Sb2Se3.

Discovery of 3-Phenyl Indazole-Based Novel Chemokine-like Receptor 1 Antagonists for the Treatment of Psoriasis.

Chemokine-like receptor 1 (CMKLR1)─a G protein-coupled receptor─has functional roles in the immune system and related diseases, including psoriasis and metabolic diseases. Psoriasis is a chronic inflammatory disease characterized by skin redness, scaliness, and itching. In this study, we sought to develop novel CMKLR1 antagonists by screening our in-house GPCR-targeting compound library. Moreover, we optimized a phenylindazole-based hit compound with antagonistic activities and evaluated its oral pharmacokinetic properties in a murine model. A structure-based design on the human CMKLR1 homology model identified S-26d as an optimized compound that serves as a potent and orally available antagonist with a pIC50 value of 7.44 in hCMKLR1-transfected CHO cells. Furthermore, in the imiquimod-induced psoriasis-like mouse model, oral administration of S-26d for 1 week significantly alleviated modified psoriasis area and severity index scores (severity of erythema, scaliness, skin thickness) compared with the control group.

Huntingtin loss in hepatocytes is associated with altered metabolism, adhesion, and liver zonation.

Huntington's disease arises from a toxic gain of function in the huntingtin (HTT) gene. As a result, many HTT-lowering therapies are being pursued in clinical studies, including those that reduce HTT RNA and protein expression in the liver. To investigate potential impacts, we characterized molecular, cellular, and metabolic impacts of chronic HTT lowering in mouse hepatocytes. Lifelong hepatocyte HTT loss is associated with multiple physiological changes, including increased circulating bile acids, cholesterol and urea, hypoglycemia, and impaired adhesion. HTT loss causes a clear shift in the normal zonal patterns of liver gene expression, such that pericentral gene expression is reduced. These alterations in liver zonation in livers lacking HTT are observed at the transcriptional, histological, and plasma metabolite levels. We have extended these phenotypes physiologically with a metabolic challenge of acetaminophen, for which the HTT loss results in toxicity resistance. Our data reveal an unexpected role for HTT in regulating hepatic zonation, and we find that loss of HTT in hepatocytes mimics the phenotypes caused by impaired hepatic ß-catenin function.

Huntingtin loss in hepatocytes is associated with altered metabolism, adhesion, and liver zonation.

Huntington's disease arises from a toxic gain of function in the huntingtin ( HTT ) gene. As a result, many HTT-lowering therapies are being pursued in clinical studies, including those that reduce HTT RNA and protein expression in the liver. To investigate potential impacts, we characterized molecular, cellular, and metabolic impacts of chronic HTT lowering in mouse hepatocytes. Lifelong hepatocyte HTT loss is associated with multiple physiological changes, including increased circulating bile acids, cholesterol and urea, hypoglycemia, and impaired adhesion. HTT loss causes a clear shift in the normal zonal patterns of liver gene expression, such that pericentral gene expression is reduced. These alterations in liver zonation in livers lacking HTT are observed at the transcriptional, histological and plasma metabolite level. We have extended these phenotypes physiologically with a metabolic challenge of acetaminophen, for which the HTT loss results in toxicity resistance. Our data reveal an unexpected role for HTT in regulating hepatic zonation, and we find that loss of HTT in hepatocytes mimics the phenotypes caused by impaired hepatic ß-catenin function.

Critical roles of metal-ligand complexes in the controlled synthesis of various metal nanoclusters.

Metal nanoclusters (NCs), an important class of nanoparticles (NPs), are extremely small in size and possess quasi-molecular properties. Due to accurate stoichiometry of constituent atoms and ligands, NCs have strong structure-property relationship. The synthesis of NCs is seemingly similar to that of NPs as both are formed by colloidal phase transitions. However, they are considerably different because of metal-ligand complexes in NC synthesis. Reactive ligands can convert metal salts to complexes, actual precursors to metal NCs. During the complex formation, various metal species occur, having different reactivity and fraction depending on synthetic conditions. It can alter their degree of participation in NC synthesis and the homogeneity of final products. Herein, we investigate the effects of complex formation on the entire NC synthesis. By controlling the fraction of various Au species showing different reactivity, we find that the extent of complex formation alters reduction kinetics and the uniformity of Au NCs. We demonstrate that this concept can be universally applied to synthesize Ag, Pt, Pd, and Rh NCs.

Development of LpxH Inhibitors Chelating the Active Site Dimanganese Metal Cluster of LpxH.

Despite the widespread emergence of multidrug-resistant nosocomial Gram-negative bacterial infections and the major public health threat it brings, no new class of antibiotics for Gram-negative pathogens has been approved over the past five decades. Therefore, there is an urgent medical need for developing effective novel antibiotics against multidrug-resistant Gram-negative pathogens by targeting previously unexploited pathways in these bacteria. To fulfill this crucial need, we have been investigating a series of sulfonyl piperazine compounds targeting LpxH, a dimanganese-containing UDP-2,3-diacylglucosamine hydrolase in the lipid A biosynthetic pathway, as novel antibiotics against clinically important Gram-negative pathogens. Inspired by a detailed structural analysis of our previous LpxH inhibitors in complex with K. pneumoniae LpxH (KpLpxH), here we report the development and structural validation of the first-in-class sulfonyl piperazine LpxH inhibitors, JH-LPH-45 (8) and JH-LPH-50 (13), that achieve chelation of the active site dimanganese cluster of KpLpxH. The chelation of the dimanganese cluster significantly improves the potency of JH-LPH-45 (8) and JH-LPH-50 (13). We expect that further optimization of these proof-of-concept dimanganese-chelating LpxH inhibitors will ultimately lead to the development of more potent LpxH inhibitors for targeting multidrug-resistant Gram-negative pathogens.

The design and synthesis of green emissive iridium(III) complexes guided by calculations of the vibrationally-resolved emission spectra.

A key challenge in developing emissive materials for organic light-emitting diodes is to optimize their colour saturation, which means targeting narrowband emitters. In this combined theoretical and experimental study, we investigate the use of heavy atoms in the form of trimethylsilyl groups as a tool to reduce the intensity of the vibrations in the 2-phenylpyridinato ligands of emissive iridium(III) complexes that contribute to the vibrationally coupled modes that broaden the emission profile. An underutilised computational technique, Frank-Condon vibrationally coupled electronic spectral modelling, was used to identify the key vibrational modes that contribute to the broadening of the emission spectra in known benchmark green-emitting iridium(III) complexes. Based on these results, a family of eight new green-emitting iridium complexes containing trimethylsilyl groups substituted at different positions of the cyclometalating ligands has been prepared to explore the impact that these substituents have on reducing the intensity of the vibrations and the resulting reduction in the contribution of vibrationally coupled emission modes to the shape of the emission spectra. We have demonstrated that locating a trimethylsilyl group at the N4 or N5 position of the 2-phenylpyridine ligand damps the vibrational modes of the iridium complex and provides a modest narrowing of the emission spectrum of 8-9 nm (or 350 cm-1). The strong correlation between experimental and calculated emission spectra highlights the utility of this computational method to understand how the vibrational modes contribute to the profile of the emission spectra in phosphorescent iridium(III) emitters.

Exploring Optimal Water Splitting Bifunctional Alloy Catalyst by Pareto Active Learning.

Design of bifunctional multimetallic alloy catalysts, which are one of the most promising candidates for water splitting, is a significant issue for the efficient production of renewable energy. Owing to large dimensions of the components and composition of multimetallic alloys, as well as the trade-off behavior in terms of the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) overpotentials for bifunctional catalysts, it is difficult to search for high-performance bifunctional catalysts with multimetallic alloys using conventional trial-and-error experiments. Here, an optimal bifunctional catalyst for water splitting is obtained by combining Pareto active learning and experiments, where 110 experimental data points out of 77946 possible points lead to effective model development. The as-obtained bifunctional catalysts for HER and OER exhibit high performance, which is revealed by model development using Pareto active learning; among the catalysts, an optimal catalyst (Pt0.15 Pd0.30 Ru0.30 Cu0.25 ) exhibits a water splitting behavior of 1.56 V at a current density of 10 mA cm-2 . This study opens avenues for the efficient exploration of multimetallic alloys, which can be applied in multifunctional catalysts as well as in other applications.

Huntingtin turnover: modulation of huntingtin degradation by cAMP-dependent protein kinase A (PKA) phosphorylation of C-HEAT domain Ser2550.

Huntington's disease (HD) is a neurodegenerative disorder caused by an inherited unstable HTT CAG repeat that expands further, thereby eliciting a disease process that may be initiated by polyglutamine-expanded huntingtin or a short polyglutamine-product. Phosphorylation of selected candidate residues is reported to mediate polyglutamine-fragment degradation and toxicity. Here to support the discovery of phosphosites involved in the life-cycle of (full-length) huntingtin, we employed mass spectrometry-based phosphoproteomics to systematically identify sites in purified huntingtin and in the endogenous protein by proteomic and phosphoproteomic analyses of members of an HD neuronal progenitor cell panel. Our results bring total huntingtin phosphosites to 95, with more located in the N-HEAT domain relative to numbers in the Bridge and C-HEAT domains. Moreover, phosphorylation of C-HEAT Ser2550 by cAMP-dependent protein kinase (PKA), the top hit in kinase activity screens, was found to hasten huntingtin degradation, such that levels of the catalytic subunit (PRKACA) were inversely related to huntingtin levels. Taken together, these findings highlight categories of phosphosites that merit further study and provide a phosphosite kinase pair (pSer2550-PKA) with which to investigate the biological processes that regulate huntingtin degradation and thereby influence the steady state levels of huntingtin in HD cells.

Enhancing Horizontal Ratio of Transition Dipole Moment in Homoleptic Ir Complexes for High Outcoupling Efficiency of Organic Light-Emitting Diodes.

The light-emitting dipole orientation (EDO) of a phosphorescent emitter is a key to improving the external quantum efficiency (EQE) of organic light-emitting diodes (OLEDs) without structural modification of the device. Here, four homoleptic Ir complexes as a phosphorescent emitter are systematically designed based on the molecular structure of tris(2-phenylpyridine)iridium(III) (Ir(ppy)3 ) to control the EDO. Trimethylsilane, methyl, 2-methylpropyl, and cyclopentylmethyl group substituted to pyridine ring of the ligand contribute to the improvement of the EDO from 76.5% for Ir(ppy)3 to 87.5%. A linear relationship between the EDO and the aspect ratio (geometric anisotropy factor) is founded, implying the importance of the effective area for the nonbonding force between host and dopant molecules. Also, it is investigated that the EDO enhancement mainly originates from the vertical alignment of the C3 axis of molecule in the substrate axis rather than the change in the direction of the transition dipole alignment in the molecular axis. The optical simulation reveals that the outcoupling efficiency of phosphorescent OLEDs adopting new dopants reaches 38.4%. The green OLEDs exhibiting 28.3% of EQE, 103.2 cd A-1 of current efficiency, and 98.2 lm W-1 of power efficiency are demonstrated, which is understood to have little electrical loss.

Observation of H2 Evolution and Electrolyte Diffusion on MoS2 Monolayer by In Situ Liquid-Phase Transmission Electron Microscopy.

Unit-cell-thick MoS2 is a promising electrocatalyst for the hydrogen evolution reaction (HER) owing to its tunable catalytic activity, which is determined based on the energetics and molecular interactions of different types of HER active sites. Kinetic responses of MoS2 active sites, including the reaction onset, diffusion of the electrolyte and H2 bubbles, and continuation of these processes, are important factors affecting the catalytic activity of MoS2 . Investigating these factors requires a direct real-time analysis of the HER occurring on spatially independent active sites. Herein, the H2 evolution and electrolyte diffusion on the surface of MoS2 are observed in real time by in situ electrochemical liquid-phase transmission electron microscopy (LPTEM). Time-dependent LPTEM observations reveal that different types of active sites are sequentially activated under the same conditions. Furthermore, the electrolyte flow to these sites is influenced by the reduction potential and site geometry, which affects the bubble detachment and overall HER activity of MoS2 .

Facile Sonochemical Synthesis of Flexible Fe-Based Metal-Organic Frameworks and Their Efficient Removal of Organic Contaminants from Aqueous Solutions.

An iron-based metal-organic framework, MIL-53(Fe), was synthesized via the simple sonochemical method, which is a facial and fast strategy, and their adsorption performance for organic contaminants removal from aqueous solutions was studied. The crystal structure and morphology analysis indicate that the sonochemical synthesis of MIL-53(Fe) particles was faster than the solvothermal preparation method, showing high crystallinity with a downsized hexagonal bipyramid shape. Furthermore, the prepared MIL-53(Fe) exhibited enhanced adsorption capability for the organic dyes compared to metal-organic framework prepared via the solvothermal method and showed excellent maximum adsorption capability for the methyl orange removal from aqueous solutions. Based on the superior adsorption properties and facile synthesis, MIL-53(Fe) prepared by ultrasound irradiation has a potential application for an efficient, economic, and ecofriendly wastewater purification process.

Genetic modifiers of Huntington disease differentially influence motor and cognitive domains.

Genome-wide association studies (GWASs) of Huntington disease (HD) have identified six DNA maintenance gene loci (among others) as modifiers and implicated a two step-mechanism of pathogenesis: somatic instability of the causative HTT CAG repeat with subsequent triggering of neuronal damage. The largest studies have been limited to HD individuals with a rater-estimated age at motor onset. To capitalize on the wealth of phenotypic data in several large HD natural history studies, we have performed algorithmic prediction by using common motor and cognitive measures to predict age at other disease landmarks as additional phenotypes for GWASs. Combined with imputation with the Trans-Omics for Precision Medicine reference panel, predictions using integrated measures provided objective landmark phenotypes with greater power to detect most modifier loci. Importantly, substantial differences in the relative modifier signal across loci, highlighted by comparing common modifiers at MSH3 and FAN1, revealed that individual modifier effects can act preferentially in the motor or cognitive domains. Individual components of the DNA maintenance modifier mechanisms may therefore act differentially on the neuronal circuits underlying the corresponding clinical measures. In addition, we identified additional modifier effects at the PMS1 and PMS2 loci and implicated a potential second locus on chromosome 7. These findings indicate that broadened discovery and characterization of HD genetic modifiers based on additional quantitative or qualitative phenotypes offers not only the promise of in-human validated therapeutic targets but also a route to dissecting the mechanisms and cell types involved in both the somatic instability and toxicity components of HD pathogenesis.

Mechanochemically Synthesized Prussian Blue for Efficient Removal of Cesium Ions from Aqueous Solutions.

The adsorptive removal of radioactive cesium [Cs(I)] is important for ensuring a clean aquatic environment. In this work, the adsorption of Cs(I) was carried out using Prussian blue (PB) prepared by mechanochemical synthesis. X-ray diffraction, Fourier-transform infrared spectroscopy, and field-emission scanning electron microscopy results indicated that PB had been successfully synthesized by mechanochemical synthesis. Thermogravimetric analysis, contact angle analysis, inductively coupled plasma atomic emission spectrometry, elemental analysis, and electrophoretic light scattering spectrophotometry confirmed that several defects were formed, explaining the principal mechanism for the efficient adsorption over PB prepared by mechanochemical synthesis. The superior adsorption properties toward Cs(I) make PB prepared by mechanochemical synthesis an attractive candidate material for the efficient, economical, and eco-friendly processes for purifying radioactive wastewater.