bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Significance of Sorbs2 in Alzheimer’s Disease
Authors: Rocco Grace , Lin Henry , Boudreau Ryan L , McLendon Jared M 
Published: January 2025

AbstractBackgroundSorbs2 is a cytoskeletal adaptor protein that is expressed in hippocampal neurons, but its mechanistic role in these cells is not yet fully understood.MethodWe created two groups of mice for our study: whole‐body Sorbs2‐Knockout (KO) mice and Sorbs2‐Flox mice, which had neuronal knockout via AAV‐PHP.eB‐hSyn1‐Cre virus injection. We assayed mixed‐sex littermate cohorts at 6 months of age (n = 24 each, WT/KO; n = 8 each ± CRE) with behavior tests. We used postmortem brain samples to visualize and quantify Sorbs2 expression and microtubule stability.ResultOur preliminary results suggest that female Sorbs2‐KO mice have a decrease in freezing time during contextual fear conditioning at 6 months of age. We next tested an independent cohort of females (n = 8v8) and the data show reduced freezing time in cued fear conditioning and decreased interaction time with the displaced object in Spatial Object Recognition tests after 24 hours. From the above‐mentioned experiments, we have collected tissue samples for molecular and histological analysis. Preliminary results show that global Sorbs2‐KO mice have a complete loss of an immunoreactive band specific to neuronal Sorbs2 isoform at ∼150 kDa, whereas AAV‐Cre injected Sorbs2‐flox mice have > 50% reduction in neuronal Sorbs2. In preliminary studies, we assessed microtubule stability in hippocampus homogenates from global Sorbs2‐KO or WT mice and showed an increase in the amount of free tubulin and a decrease in the amount of polymerized tubulin in the knockout samples. These data suggest that loss of Sorbs2 may destabilize microtubules in the hippocampus.ConclusionOur results suggest that Sorbs2 may regulate microtubule stability in the brain and be involved in memory formation or retrieval. In future studies, we plan to identify populations of Sorbs2‐expressing cells in the brain, interrogate neuronal‐specific Sorbs2 deletion, and assess the intersection between Sorbs2 and AD‐related phenotypes in mouse models of neurodegeneration.
Targeting cannabinoid type 2 receptors alters human tau levels in ex vivo brain slice cultures
Authors: Joers Valerie L , Bagheri Ila , Coronado Jazmyn , Hillard Cecilia , Tansey Malu Gámez 
Published: January 2025

AbstractBackgroundThe presence of Tau pathology is strongly associated with the clinical symptoms and cognitive decline found in Alzheimer’s disease (AD), suggesting that targeting pathological tau may be a more effective therapeutic approach. Microglia have been implicated in tauopathies as their activation is strongly related to the progression of tau phosphorylation and aggregation potentially due to dysfunctional lysosomal activity. Cannabinoid type 2 receptors (CB2) are highly expressed in immune cells and upregulated in activated microglia under conditions of neurologic disease, such as AD. CB2 deficient models have demonstrated a reduction in inflammation and amyloid plaque deposition, suggesting a role of CB2 on the immune system to influence AD‐related pathologies. However, there are limited findings on the CB2 regulation of tau accumulation.MethodWe have generated organotypic brain slice cultures from CB2‐EGFP/f/f and CB2‐knockout mice and transduced with human wild‐type and mutant (P301L or P301L/S320F) tau viruses, previously shown to accumulate total and phosphorylated human tau and develop insoluble tau aggregates. As a complimentary approach, slices were treated with CB2‐selective ligands. Slices were evaluated for tau aggregation and microglial phenotypes using biochemical fractionation and western immunoblotting analyses.ResultIn our hands, brain slice cultures overexpressing human P301L‐tau generate soluble total and phosphorylated tau species but do not produce urea‐soluble aggregates. Our preliminary work demonstrated that P301L expressing brain slice cultures deficient in CB2 do not have altered high‐salt soluble total or phosphorylated tau compared to CB2‐EGFP/f/f slices. Yet, treatment with CB2 inverse agonist SR144528 reduced phosphorylated tau (Ser202/Thr205) in the soluble fraction (p = 0.0011) in CB2‐EGFP/f/f brain slices over‐expressing P301L/S320F human tau compared to vehicle treatment. Further evaluations on tau aggregation are being conducted on brain slice cultures from CB2‐EGFP/f/f and CB2‐knockout mice overexpressing P301L/S320F tau.ConclusionThese results suggest that CB2 alters the function of immune cells to reduce tau species in a stimulation dependent‐manner. Future studies will evaluate microglia‐restricted CB2 knock‐out brain slices to advance our understanding of the role of brain CB2 in the microglial contribution to pathologic tau removal and potentially highlight CB2 as a therapeutic target against tauopathies.
Measurements of decision‐making ability in middle to late adulthood: a multi domain scoping review from the ARMCADA study
Authors: Ho Emily , Ece Berivan , Hosseinian Zahra , Mather Molly A , Dworak Elizabeth , Novack Miriam , Karpouzian‐Rogers Tatiana , Pila Sarah , Weintraub Sandra , Gershon Richard C. 
Published: January 2025

AbstractBackgroundDeficits in decision‐making (DM) can lead to adverse outcomes across multiple domains such as financial management and medical care. By hindering such DM abilities, cognitive impairment (CI) often affects quality of life. Routine screening for CI, however, does not include systematic and comprehensive assessment of DM ability. While there are many measures of DM ability, there is considerable heterogeneity in what constructs are measured and the populations in which they have been validated. This scoping review assessed what decision‐making measures were present in the literature and their validation evidence, across the domains of financial, functional outcomes, health care, end‐of‐life, and affective.MethodWe adhered to established scoping review methodology and included keywords pertaining to measurement, technology, decision‐making, and age across a variety of databases. A total of 16278 articles were identified, and of those, 1654 passed title and abstract screening, and were deemed eligible for full‐text review. Seven‐hundred eighty six studies were included for consideration of full‐text extraction; currently, 581 were identified for full‐text extraction.ResultPreliminary findings suggest that across domains, there were more measures for functional outcomes (25%), health‐care decision‐making (19%), followed by financial decision‐making (15%), affective (15%), and end‐of‐life (3%), though there were many measures rated as encompassing more than one category. Measures are overwhelmingly in‐person (69%), while 16% could be administered remotely, although many of them were computer‐based tasks. Common decision‐making tasks included tests of risk (e.g., gambling tasks), semi‐structured interviews of assessment, and brief cognitive screenings. Such measures were presented with a variety of clinical populations.ConclusionMany measures of decision‐making ability identified were used in laboratory or research settings, or measured one construct. Future work will investigate adaptation, validation, and development of existing decision‐making measures, for early detection of preclinical dementia.
Evaluation of novel metrics derived from a brief smartphone cognitive task for predicting disease severity in frontotemporal dementia
Authors: Taylor Jack C. 
Published: January 2025

AbstractBackgroundSensitive assessments capable of detecting cognitive changes are important for improving early identification of symptoms in frontotemporal dementia (FTD). The ALLFTD Mobile App features smartphone cognitive tests that capture a range of FTD symptoms. We have previously shown that the flanker task from this battery is reliable and capable of detecting early changes in FTD. Here we generate features from the digital flanker task and utilize machine learning algorithms to test their incremental utility for detecting cognitive changes in FTD.MethodSample included 50 symptomatic and 70 prodromal, sporadic and familial FTD participants (CDR®+NACC‐FTLD = 1 or 0.5, respectively) with a range of FTD syndromes, and 70 controls (CDR®+NACC‐FTLD = 0, no pathogenic mutation) from the ALLFTD Consortium. Participants completed a two‐minute, 100‐trial digital flanker assessment on the ALLFTD Mobile App. We extracted 301 distribution metrics, based on reaction time and trial type, and 15 traditional metrics using an in‐house pipeline. Random forest models were trained using 5‐fold cross validation to classify controls from prodromal or from symptomatic individuals. The top 10 metrics of importance based on SHAP value were then entered as predictors in a standard logistic regression model and compared to a logistic model including only total score (speed + accuracy) as the predictor.ResultIn all comparisons, logistic regressions achieved higher classification accuracies than the random forest models. When using random forest to classify controls vs prodromal and controls vs symptomatic, AUCs were 0.69 and 0.81, respectively. Logistic model AUCs for classifying controls vs prodromal were 0.85 using total score alone and 0.81 using all top 10 metrics. When classifying controls vs symptomatic, model AUCs were 0.84 using total score alone and 0.91 using all top 10 metrics.ConclusionWe tested the use of experimental features derived from a brief two‐minute test to distinguish healthy individuals from prodromal or symptomatic FTD. Classification accuracies were moderate to high, suggesting that while traditional measures continue to perform well, novel features provide an improvement in accuracy. Future directions include analogous investigations of other smartphone cognitive tasks collected through this battery.
Persistent DNA damage response drives cGAS‐STING mediated neuroinflammation in a mouse model of tauopathy
Authors: Singh Himanshi , Xiao Jianfeng , Khan Sazzad , Das Asmita , Pourmotabbed Tayebeh , Khan Mohammad Moshahid 
Published: January 2025

AbstractBackgroundTauopathies are a group of neurological disorders including Alzheimer’s disease that involve progressive neurodegeneration, behavioral deficits, and aberrant tau accumulation. While the molecular mechanisms that regulate the progression of the tauopathy are not fully elucidated, there is evidence to suggest that accumulation of nuclear DNA damage, particularly nuclear DNA double‐strand breaks (DNA DSBs), contribute to the progression of neurodegeneration. In our present work, we investigated the relationship between DNA DSB accumulation and neuroinflammation in the brains of AD patients and a mouse model of tauopathy.MethodWe used multiple approaches including ELISA, RT‐qPCR, Western blot and immunohistochemistry to examine the DNA DSB expression and DNA repair function in the entorhinal cortex of human AD and non‐AD brains.ResultIn comparison to non‐AD subjects, we found increased g‐H2A.X (Ser139) a biomarker of DNA DSB and reduced expression levels of DNA repair proteins in the entorhinal cortex of human AD brains. This was positively correlated with upregulation of cyclic GMP‐AMP synthase (cGAS) and stimulator of interferon genes (STING) immune regulatory pathway, and tau pathology. Next, we observed higher amounts of DNA DSB and altered expression levels of DNA repair proteins in the brains of PS19Tg mice as compared to non‐Tg mice. Our results showed that increased DNA DSBs and reduced expression of DNA repair proteins were further associated with significant increase in cGAS‐STING pathway.ConclusionThese results offered strong evidence that tauopathy is linked to DNA DSB accumulation and/or changes in DNA repair proteins, which may have an impact on a critical initial step of the process, such as neuroinflammation, leading to neurodegeneration and memory loss.
Effect of Oil Shale Semi‐Coke With Different Particle Sizes on Mechanical and Thermal Properties of Low‐Density Polyethylene Composites
Authors: Zhang Xuejian , Wang Kuishan , Li Weina , Li Yongtao , Ai Weidong , Liu Huisheng , Huang Dexin , Chang Yushuo , Chen Angchen 
Published: January 2025

ABSTRACTThis study explores the feasibility of utilizing oil shale semi‐coke powder as a substitute for heavy calcium carbonate powder in low‐density polyethylene (LDPE). Initially, oil shale semi‐coke with varying particle sizes is produced by adjusting the ball milling time. Subsequently, LDPE composites with different filler weight fractions are prepared using an internal mixer. The effects of particle size and filler weight fractions on the composites are investigated. The tensile strength of the composites significantly increases with a reduction in the particle size of the oil shale semi‐coke and also increases with an increasing filler weight fraction. Based on the analysis of interface interaction parameters and fracture morphology, it is found that the oil shale semi‐coke with a ball milling time of 40 min exhibits the best particle dispersion. Thermogravimetric analyses demonstrate that the composites made with oil shale semi‐coke have better hot‐air stability. Notably, the composites filled with a 29.70% weight fraction of oil shale semi‐coke and a ball milling time of 40 min achieve the highest crystallinity and the smallest grain size, aligning with the observed mechanical properties.
Abnormalities in cerebellar subregions' volume and cerebellocerebral structural covariance in autism spectrum disorder
Authors: Wang Yu , Cao Aihua , Wang Jing , Bai He , Liu Tianci , Sun Chenxi , Li Zhuoran , Tang Yuchun , Xu Feifei , Liu Shuwei 
Published: January 2025

AbstractThe cerebellum plays a crucial role in functions, including sensory‐motor coordination, cognition, and emotional processing. Compared to the neocortex, the human cerebellum exhibits a protracted developmental trajectory. This delayed developmental timeline may lead to increased sensitivity of the cerebellum to external influences, potentially extending the vulnerability period for neurological disorders. Abnormal cerebellar development in individuals with autism has been confirmed, and these atypical cerebellar changes may affect the development of the neocortex. However, due to the heterogeneity of autism spectrum disorder (ASD), the regional changes in the cerebellum and cerebellocerebral structural relationship remain unknown. To address these issues, we utilized imaging methods optimized for the cerebellum and cerebrum on 817 individuals aged 5–18 years in the ABIDE II dataset. After FDR correction, significant differences between groups were found in the right crus II/VIIB and vermis VI‐VII. Structural covariance analysis revealed enhanced structural covariance in individuals with autism between the cerebellum and parahippocampal gyrus, pars opercularis, and transverse temporal gyrus in the right hemisphere after FDR correction. Furthermore, the structural covariance between the cerebellum and some regions of the cerebrum varied across sexes. A significant increase in structural covariance between the cerebellum and specific subcortical structures was also observed in individuals with ASD. Our study found atypical patterns in the structural covariance between the cerebellum and cerebrum in individuals with autism, which suggested that the underlying pathological processes of ASD might concurrently affect these brain regions. This study provided insight into the potential of cerebellocerebral pathways as therapeutic targets for ASD.
“Water in Ionic Liquid” Electrolyte Toward Supercapacitors With High Operation Voltage, Long Lifespan, and Wide Temperature Compatibility
Authors: Yang Yibing , Liu Min , Zhang Dongliang , Wu Shuilin , Zhang Wenjun 
Published: January 2025

ABSTRACTAqueous electrolytes, with their inherent safety, low cost, and eco‐friendliness, provide a promising alternative for energy storage devices, but their application is limited due to the narrow electrochemical stability window of water. Using super‐concentrated electrolytes has been demonstrated effectives in expanding the electrochemical window of aqueous electrolytes. However, this approach also brings in several challenges, including decreased ionic conductivity, poor wettability, and increased temperature sensitivity due to the near‐saturated salt concentrations. In this study, we employed a water‐miscible ionic liquid (i.e., 1‐butyl‐3‐methylimidazolium trifluoromethanesulfonate) to break the solubility limitations faced in super‐concentrated electrolytes and created a new “water in ionic liquid” electrolyte that simultaneously featured with broad electrochemical window, decent ionic conductivity, and wide temperature compatibility. Moreover, a prototype of electrochemical double‐layer supercapacitor utilizing the “water in ionic liquid” electrolyte demonstrates outstanding performance characteristics, including a high operating voltage (2.6 V), excellent rate capability with 81% capacitance retention from 0.5 to 30 A g–1, remarkable cyclic stability with 75% capacitance retention after 120,000 cycles, along with broad temperature compatibility from –20°C to 60°C. These findings not only provide new insights into electrolyte engineering but also offer a pathway for designing innovative aqueous electrolytes for energy storage devices with balanced electrochemical performance.
Photoresponsive Helical Foldamers: Conformational Control Through Double Helix Formation and Light‐Induced Protonation
Authors: Hardoin Louis , Kdouh Rana , Aidibi Youssef , Azar Soussana , Siegler Benjamin , Allain Magali , Goeb Sébastien , Levillain Eric , Bouit Pierre‐Antoine , Galangau Olivier , Sallé Marc , Canevet David 
Published: January 2025

AbstractHelical foldamers constitute particularly relevant targets in the field of host‐guest chemistry, be that as hosts or substrates. In this context, the strategies reported so far to control the dimensions and shape of foldamers mainly involve modifications of the skeleton through covalent synthesis. Herein, we prepared an oligopyridine dicarboxamide foldamer substituted by photo‐active tetraphenylethylene units (TPE). We demonstrate that it is possible to toggle the length of a helical foldamer by two means. First, the elongation of foldamers can be tuned by adjusting the concentration, as demonstrated by DOSY NMR spectroscopy and X‐ray diffraction analyses on both the single and the double helix structures. Secondly, and in a more original manner, a photo‐induced protonation process triggered by TPE units promotes a novel pathway to unfold helical foldamers, leading to dramatic conformational and spectroscopic changes.
Synthesis of Vinyl Sulfones from Substituted Alkenes via Molybdooxaziridine Catalysis
Authors: Doran Erin L. , Doran Jenna M. , Pinarci Ali A. , Rossi Morgan E. , Madiu Rufai , Howard Amari M. , Stroud James L. , Rivera Dominic A. , Moskovitz Dylan A. , Singer Alyssa N. , Finneran Steven J. , Moura‐Letts Gustavo 
Published: January 2025

AbstractHerein we report the MoO2Dipic promoted sulfonation of alkenes using N−Ts‐hydroxylamine as the quantitative source of Ts. The reaction works with high yields and stereoselectivities for styrenes with a wide variety of substitution patterns. A novel atom transfer radical addition mechanism involving the formation of molybdooxaziridine complex 1 as the active catalyst, difunctionalization with Ts‐NO, followed by oxidation, and then elimination as the rate‐determining‐step for the formation of vinylsulfone 3 has been proposed. Initial kinetic and mechanistic data indicates the formation of Ts‐NO and provides evidence for the proposed mechanism.
A Consecutive Genome Engineering Method Reveals a New Phenotype and Regulation of Glucose and Glycerol Utilization in Clostridium Pasteurianum
Authors: Nguyen Tom , Meleski Luca W. G. , Belavatta Minu P. , Gurumoorthi Sivasubramanian , Zhang Chijian , Heins Anna‐Lena , Zeng An‐Ping 
Published: January 2025

ABSTRACTClostridium pasteurianum is a microorganism for production of 1,3‐propanediol (1,3‐PDO) and butanol, but suffers from lacking genetic tools for metabolic engineering to improve product titers. Furthermore, previous studies of C. pasteurianum have mainly focused on single genomic modification. The aim of this work is the development and application of a method for modification of multiple gene targets in the genome of C. pasteurianum. To this end, a new approach for consecutive genome engineering is presented for the first time using a method based on endogenous CRISPR‐Cas machineries. A total of three genome modifications were consecutively introduced in the same mutant and the effect of combined changes on the genome was observed by 39% decreased specific glycerol consumption rate and 29% increased 1,3‐PDO yield in mixed substrate fermentations at laboratory scale in comparison to the wildtype strain. Additionally, examination of the phenotype of the generated mutant strain led to discovery of 2,3‐butanediol (2,3‐BDO) production of up to 0.48 g L−1, and this metabolite was not reported to be produced by C. pasteurianum before. The developed procedure expands the genetic toolkit for C. pasteurianum and provides researchers an additional method which contributes to improved genetic accessibility of this strain.
Investigating Ultrafiltration Membranes and Operation Modes for Improved Lentiviral Vector Processing
Authors: Labisch Jennifer J. , Evangelopoulou Maria , Schleuß Tobias , Pickl Andreas 
Published: January 2025

ABSTRACTThe demand for lentiviral vectors (LVs) as tools for ex vivo gene therapies is ever‐increasing. Despite their promising applications, challenges in LV production remain largely due to the fragile envelope, which challenges the maintenance of vector stability. Thus, downstream processing optimization to enhance efficiency, yield, and product quality is necessary. This study investigated the influence of membrane types and filtration devices during ultrafiltration (UF). Nine different membrane materials consisting of polyethersulfone (PES), regenerated cellulose, or Hydrosart, with distinct molecular weight cutoffs, were evaluated in stirred cells, centrifugal ultrafilters, and crossflow cassettes. The evaluation was based on the ability to retain infectious LV particles and remove impurities. The analysis revealed that a reinforced 100 kDa PES and a 300 kDa Hydrosart membrane had the best overall ability to concentrate infectious LVs and remove DNA, especially when operated in a stirred cell. Challenges were seen in the nonoptimized crossflow cassette process, where infectious LV recovery was generally lower compared to other devices. We demonstrated that membrane material and filtration device have a direct impact on the efficiency of LV UF.