Aggregated Form Research Articles

Sedimentology of False Bay (Western Cape, South Africa): geological background information for the integrated environmental management of a physically confined coastal compartment

Abstract False Bay is a large, physically confined embayment located along the southwest coast of South Africa. It is a classic example of a coastal compartment or littoral cell that acts as a receptor and sink of both terrestrial (siliciclastic) and marine (bioclastic) material. It is almost square in shape, measuring ∼35 km N-S and ∼39 km W-E and covering ∼1130 km2. Only a few small rivers discharge into the bay, as a consequence of which only small amounts of sediment are episodically supplied to the bay. The bathymetry reveals two well-defined terraces, one between 30 and 45 m, the other between 50 and 55 m water depth, which are indicative of extended Pleistocene sea-level stillstands. Sediment is dispersed by long-period ocean swells approaching from the southwestern quadrant, as well as nearshore swell- and wind-driven currents. The presence of a prominent rock pinnacle at the entrance to the bay (Rocky Bank) causes wave orthogonals to converge on its leeward side, and which results in substantial wave amplification along the eastern shore of the bay. Coarse-grained sediments (gravel, very coarse sand, coarse sand and medium sand) line the rocky shores in the west and east, and are dispersed around and away from submarine rock outcrops, whereas fine-grained sediments (fine sand, very fine sand and mud) are largely confined to an arcuate belt extending along the centre of the bay from shallow water in the northwest to the deepest parts in the south. This is documented by the distribution of individual size fractions and the mean grain size, and applies to both the siliciclastic and the bioclastic sediment components which appear to be in hydraulic equilibrium. There is a distinct N-S gradient from lower to higher bioclastic content with increasing water depth. The textural parameters (mean grain size, sorting and skewness) reveal the existence of two hydraulic populations that are mixed in various proportions in the course of their dispersal in the form of either bed load or suspended load transport. The mud fraction is closely linked to the dispersal pattern of the fine and very fine sand fractions, indicating that it is transported in the form of aggregates and/or faecal pellets, the bulk of which is evidently in hydraulic equilibrium with the finer-grained sands. It can be anticipated that, during lower Pleistocene sea levels, the palaeo-False Bay valley was occupied, or at least regularly visited, by large and small African mammals and early humans.

Reactivity of chondritic meteorites under H2-rich atmospheres: Formation of H2S.

Abstract Current models of chemical evolution during star and planetary formation rely on the presence of dust grains to act as a third body. However, they generally ignore the reactivity of the dust grains themselves. Dust grains present in the protoplanetary phase will evolve as the solar system forms and, after protoplanets have appeared, they will be constantly delivered to their surfaces in the form of large aggregates or meteorites. Chondritic meteorites are mostly unaltered samples of the dust present in the first stages of the Solar System formation, that still arrive nowadays to the surface of Earth and allow us to study the properties of the materials forming the early Solar System. These materials contain, amongst others, transition metals that can potentially act as catalysts, as well as other phases that can potentially react in different astrophysical conditions, such as FeS. In this work, we present the reactivity of chondritic meteorites under H2-rich atmospheres, particularly towards the reduction of FeS for the formation of H2S and metallic Fe during the early phases of the planetary formation. We present the obtained results on the reaction rates and the percentage of FeS available to react in the materials. Additionally, we include a computational study of the reaction mechanism and the energetics. Finally, we discuss the implications of an early formation of H2S in planetary surfaces.

α-Synuclein plastic antibody applied to monitor monomeric structures and discriminate aggregated forms in human CSF

Aggregation of alpha-synuclein (aSyn) occurs in presynaptic neurons and constitutes a key factor for the progression of Parkinson's disease, emphasising the urgency of early detection to support effective treatment. Unfortunately, a reliable, sensitive and cost-effective diagnostic tool has so far been lacking.Thus, this work presents a novel biosensor for detecting aSyn using plastic antibodies coupled to electrochemical detection. This biosensor was designed for portability and compatibility with point-of-care devices and exploits the electropolymerization of methylene blue (MB) together with aSyn on the carbon working electrode of screen-printed electrodes (SPEs). By electrochemical impedance spectroscopy (EIS) measurements, the sensor showed exceptional analytical performance in detecting aSyn monomers in human CSF samples. It showed a linear trend of response from 1 fM to 10 pM with an impressively low limit of detection of 69 aM. Selectivity tests confirmed the predominant response to aSyn monomers, a less intense response to oligomers and insensitivity to fibrils.Overall, this plastic antibody-based electrochemical sensor represents a significant breakthrough as it is the first of its kind to accurately, sensitively and selectively detect aSyn monomers with a partial response to oligomers. Its simplicity and reproducibility promise to contribute to the early and effective diagnosis of Parkinson's disease.

New insights into microalgal photobiological hydrogen production: Potential role of aggregation forms in modulating the hydrogenase activity and metabolic properties of microalgae during hydrogen production

Photobiological hydrogen production of microalgae is highly influenced by environmental conditions, and the appropriate microalgal aggregation form is conducive to microalgae overcome environmental limitations and increase their hydrogen production capacity. In this study, the effects of three aggregation methods including self-flocculation, biofilm attachment, and gel immobilization on the photobiological hydrogen production of both prokaryotic Synechocystis sp. and eukaryotic Chlamydomonas reinhardtii were investigated. The results indicated that microalgal aggregates formed via gel immobilization exhibited superior physicochemical properties such as porosity, integrity, and oxygen diffusion coefficients, creating favorable conditions for enhanced hydrogenase activity. Upon gel-immobilization, hydrogen production of Synechocystis sp. and C. reinhardtii exhibited an increase of 1.89 and 2.02-folds, respectively, compared with suspended microalgae. Concurrently, hydrogenase activities increased to 2.07 and 32.9 H2/(mg chlorophyll·h), respectively. The gel-immobilized aggregate form prompted the microalgae to maintain a relatively high photosynthetic activity, with the electron transfer rate reaching more than 1.58 folds of the control. Notably, three aggregated forms also accelerated oxygen consumption, and intracellular organic matter degradation, thereby optimizing electron utilization by microalgal hydrogenase. Furthermore, aggregation up-regulated hydrogenase gene expression in both species, particularly in gel-immobilized groups (2.34- and 4.14-folds increase compared with the control for Synechocystis sp. and C. reinhardtii, respectively). Subsequently, significantly upregulated gene expression related to oxidative phosphorylation and antioxidant systems was observed in C. reinhardtii aggregates, correlating with its relatively higher increase in hydrogen production compared with Synechocystis sp. aggregates. This study elucidated the mechanism by which aggregation strengthens microalgal hydrogen production and offers insights crucial for its industrialization.

Possibility of short synthetic peptides with activities of suppressing amyloid β aggregation and resolving its aggregated form as therapeutic drugs for Alzheimer's disease

Lecanemab is a new anti-amyloid antibody being developed as a treatment for Alzheimer's disease. It is expected to delay the progression of the disease by reducing the accumulation of amyloid beta (Aβ) in the brain. However, no drug has been developed that can completely eliminate Aβ and improve symptoms. A representative Catalytide, JAL-TA9 (YKGSGFRMI), cleaves Aβ42 and improves symptoms in an Alzheimer's disease mouse model, suggesting that JAL-TA9 is a promising candidate for treating Alzheimer's disease by effectively eliminating Aβ. The catalytic center of JAL-TA9 is GSGFR. To identify better Catalytides for Alzheimer's treatment, we analyzed the structure-activity relationship of 21 point-mutated GSGFR derivatives. In this process, we discovered two peptides, GSGFK and GSGNR, that not only inhibit Aβ25-35 aggregation but also dissolve aggregated Aβ25-35. Intracerebroventricular administration of GSGFK protected mice against Aβ25-35-induced short-term memory deficits and promoted microglial phagocytic activity. Like Lecanemab, GSGFK targets Aβ, but it has advantages such as safety, administration method, and cost. In this talk, we will discuss the potential of GSGFK as a therapeutic candidate for Alzheimer's disease.

The use of PROMs (patient-reported outcome measures) and PREMs (patient-reported experience measures) in Cardiology: current state and applications to improve patient care

The integration of patient-reported outcomes and experiences through PROMs and PREMs tools represents a significant evolution in the quality of care and clinical practice. This article reviews the state of the art and the application experiences of these tools, focusing on their impact on the management of cardiovascular diseases. The use of PROMs and PREMs allows for a more comprehensive assessment of patient well-being by integrating with traditional clinical indicators. An increasing number of studies suggests that the systematic collection of these data can help physicians in better identifying individual patient's needs, improving doctor-patient communication, and personalizing therapies. In aggregate form, these data can be used to improve the quality of services. This article explores the main international experiences, starting from the activities carried out in this field by the European Society of Cardiology, the challenges in implementing such tools, and the prospects for a more widespread adoption in daily clinical practice. It emphasizes the activities carried out in Italy by the Fondazione Toscana Gabriele Monasterio and the Management and Healthcare Laboratory of the Scuola Superiore Sant'Anna of Pisa, highlighting the importance of validated tools, appropriate technologies, and a cultural change to promote patient-centered care.

Aggregation Dynamics of a 150 kDa Aβ42 Oligomer: Insights from Cryo Electron Microscopy and Multimodal Analysis

Protein misfolding is a widespread phenomenon that can result in the formation of protein aggregates, which are markers of various disease states, including Alzheimer's disease (AD). In AD, amyloid beta (Aβ) peptides are key players in the disease's progression, particularly the 40- and 42 residue variants, Aβ40 and Aβ42. These peptides aggregate to form amyloid plaques and contribute to neuronal toxicity. Recent research has shifted attention from solely Aβ fibrils to also include Aβ protofibrils and oligomers as potentially critical pathogenic agents. Particularly, oligomers demonstrate more significant toxicity compared to other Aβ specie. Hence, there is an increased interest in studying the correlation between toxicity and their structure and aggregation pathway. The present study investigates the aggregation of a 150kDa Aβ42 oligomer that does not lead to fibril formation. Using negative stain transmission electron microscopy (TEM), size exclusion chromatography (SEC), dynamic light scattering (DLS), and cryo-electron microscopy (cryo-EM), we demonstrate that 150kDa Aβ42 oligomers form higher-order string-like assemblies over time. These strings are unique from the classical Aβ fibrils. The significance of our work lies in elucidating molecular behavior of a novel non-fibrillar form of Aβ42 aggregate.

A Fractal Study on Random Distribution of Recycled Concrete and Its Influence on Failure Characteristics

In order to quantitatively describe the influence of aggregate distribution on crack development and peak stress of recycled aggregate concrete, a multifractal spectrum theory was proposed to quantitatively characterize aggregate distribution in specimens. A mesomechanical model of reclaimed aggregate concrete mixed with natural aggregate and artificial aggregate was constructed. Numerical simulation tests were conducted on the uniaxial compression mechanical behavior of 25 groups of sample models with the same proportion and different aggregate distribution forms. Based on the box dimension theory, the multiple fractal spectrum method was used to quantitatively characterize the aggregate distribution form, and the key factors affecting cracks were explored based on the gray correlation degree. The research results show that the aggregate distribution in recycled aggregate concrete has multifractal characteristics. The multifractal spectrum was used to effectively characterize the aggregate distribution pattern, which can enlarge local details and provide new ideas for the quantitative analysis of the damage mode of recycled concrete. Secondly, by establishing a statistical model of the correlation between the multifractal spectrum width of the aggregate distribution pattern and the crack distribution box dimension, it was found that there was a positive correlation between the two, that is, the greater the multifractal spectrum width of the aggregate distribution pattern, the greater the crack box dimension, and the more complex the crack distribution. The complexity of aggregate distribution is closely related to the irregularity and complexity of mesoscopic failure crack propagation in recycled concrete specimens. In addition, gray correlation theory was applied to analyze the key factors affecting the formation of cracks in the specimens. The results showed that aggregate distribution had a first-order correlation with crack formation, and changes in aggregate distribution were an important factor affecting the performance of recycled concrete. Secondly, the poor mechanical properties of NAITZ led to obvious material damage, while NCA and MZ had a significant impact on the skeleton effect in the stress–strain process due to their large areas. This study deepens people’s understanding of the damage characteristics and cracking failure modes of recycled concrete. The study verifies the feasibility of the application of recycled aggregates and provides a valuable reference for engineering practice.

Taiwan’s scientific collaboration under the New Southbound Policy: Trends, effects, mechanisms, and implications

My dissertation explores the evolving trends and patterns in Taiwan’s scientific collaboration under the New Southbound Policy (NSP), with a focus on research co-authorship with NSP target countries across Southeast and South Asia, as well as Australia and New Zealand. Launched in 2016, the NSP represents Taiwan’s strategic effort to reintegrate into the Indo-Pacific region amidst shifting geopolitical realities. This study investigates the underexplored dynamics of scientific collaboration and the seldom-tested policy effects in a non-Western, non-colonial context, exemplifying science diplomacy in action. Specifically, this research addresses three key questions: (1) What are the long-term trends in research collaboration with NSP target countries from the mid-2000s to 2021? (2) How do co-authorship patterns and dynamics manifest in cross-specialization profiles and authorship orders among these countries? (3) What impact has the NSP had on the volume of co-authored research? Methodologically, this study combines bibliometric, network, and modeling approaches. It employs established bibliometric indicators for measuring attractiveness and preferences among partnered countries, multilayer network analysis, and piecewise models of change. The primary data sources are drawn from Clarivate’s Web of Science, accessed in both aggregated forms via the Observatoire des sciences et des technologies and as raw JSON data retrieved through the Web of Science Expanded API. By analyzing the patterns, effects, and mechanisms of Taiwan’s scientific collaboration with NSP target countries, this dissertation contributes to broadening theories and methodologies of international scientific collaboration. It also sheds light on South–South collaboration and offers policy implications for nations navigating similar geopolitical challenges.

Synthesis of Mo-Cu nanocomposite powder by hydrogen reduction of copper nitrate coated MoO3 powder mixture

The fabrication of Mo-based nanocomposite powder with homogeneous dispersion of Cu was investigated. The fine MoO3 powders were prepared by high energy ball milling, and Cu particles on the ball-milled powder surfaces were formed by calcination of a precursor solution copper nitrate. In the powder mixture calcined at 300 °C, MoO3 and CuO appeared in the form of aggregates with fine particles. Microstructural analysis showed that the oxide powders were changed to Mo-Cu nanocomposite powders with an average particle size of about 150 nm and had microstructural homogeneity by hydrogen reduction at 800 °C for 1 h. These results are help to optimize the synthesis process of homogeneous Mo-Co nanocomposite powders.

Biofilm matrix: a multifaceted layer of biomolecules and a defensive barrier against antimicrobials.

Bacterial cells often exist in the form of sessile aggregates known as biofilms, which are polymicrobial in nature and can produce slimy Extracellular Polymeric Substances (EPS). EPS is often referred to as a biofilm matrix and is a heterogeneous mixture of various biomolecules such as polysaccharides, proteins, and extracellular DNA/RNA (eDNA/RNA). In addition, bacteriophage (phage) was also found to be an integral component of the matrix and can serve as a protective barrier. In recent years, the roles of proteins, polysaccharides, and phages in the virulence of biofilms have been well studied. However, a mechanistic understanding of the release of such biomolecules and their interactions with antimicrobials requires a thorough review. Therefore, this article critically reviews the various mechanisms of release of matrix polymers. In addition, this article also provides a contemporary understanding of interactions between various biomolecules to protect biofilms against antimicrobials. In summary, this article will provide a thorough understanding of the functions of various biofilm matrix molecules.

Analysis of geographical distribution of high-grade glioma diagnoses in the Alessandria province: pilot study preliminary results

Background: one under-researched line of investigation is gliomas, which are a group of malignant brain tumours with highly poor prognoses. Despite efforts to identify environmental risk factors for gliomas, their etiology still remains unclear. It turns out that several future developments are needed in order to understand other potential risk factors. To this end, the primary objective of the present pilot study is to conduct an assessment of the spatial distribution of high-grade brain tumor cases in the province of Alessandria, where possible risk factors such as the presence of chemical industries and asbestiform fibers are found. Materials and Methods: the study sample consisted of all patients diagnosed with high-grade glioma between January 2018 and April 2023, residents in the province of Alessandria at the time of diagnosis and referred to the health facilities of the "Azienda Sanitaria Locale di Alessandria" and the "Azienda Universitario-Ospedaliera di Alessandria". Biographical and pathological history variables were collected, and finally, data were processed in aggregate and anonymized form. A total of 103 deceased patients were enrolled, stratified by age and type of diagnosis. Results: it was seen that the city with the most cases was Alessandria, with 27 diagnoses found during the period under review (26.2%), followed by cities of Acqui Terme, Casale Monferrato, and Novi Ligure with seven diagnoses (6.8%). Preliminary results presented in this paper were compared with data already published. Conclusions: analyses performed to arrive at an initial geographical distribution of high-grade glioma diagnoses are consistent relative to the population density of each municipality considered.

Formulation Strategies to Overcome Amphotericin B Induced Toxicity.

Fungal infection poses a major global threat to public health because of its wide prevalence, severe mortality rate, challenges involved in diagnosis and treatment, and the emergence of drug-resistant fungal strains. Millions of people are getting affected by fungal infection, and around 3.8 million people face death per year due to fungal infection, as per the latest report. The polyene antibiotic AmB has an extensive record of use as a therapeutic moiety against systemic fungal infection and leishmaniasis since 1960. AmB has broad-spectrum fungistatic and fungicidal activity. AmB exerts its therapeutic activity at the cellular level by binding to fungal sterol and forming hydrophilic pores, releasing essential cellular components and ions into the extracellular fluid, leading to cell death. Despite using AmB as an antifungal and antileishmanial at a broad scale, its clinical use is limited due to drug-induced nephrotoxicity resulting from binding the aggregated form of the drug to mammalian sterol. To mitigate AmB-induced toxicity and to get better anti-fungal therapeutic outcomes, researchers have developed nanoformulations, self-assembled formulations, prodrugs, cholesterol- and albumin-based AmB formulations, AmB-mAb combination therapy, and AmB cochleates. These formulations have helped to reduce toxicity to a certain extent by controlling the aggregation state of AmB, providing sustained drug release, and altering the physicochemical and pharmacokinetic parameters of AmB. Although the preclinical outcome of AmB formulations is quite satisfactory, its parallel result at the clinical level is insignificant. However, the safety and efficacy of AmB therapy can be improved at the clinical stage by continuous investigation and collaboration among researchers, clinicians, and pharmaceutical companies.

Comparison of Survivin Determination by Surface-Enhanced Fluorescence and Raman Spectroscopy on Nanostructured Silver Substrates.

Survivin belongs to a family of proteins that promote cellular proliferation and inhibit cellular apoptosis. Its overexpression in various cancer types has led to its recognition as an important marker for cancer diagnosis and treatment. In this work, we compare two approaches for the immunochemical detection of survivin through surface-enhanced fluorescence or Raman spectroscopy using surfaces with nanowires decorated with silver nanoparticles in the form of dendrites or aggregates as immunoassays substrates. In both substrates, a two-step non-competitive immunoassay was developed using a pair of specific monoclonal antibodies, one for detection and the other for capture. The detection antibody was biotinylated and combined with streptavidin labeled with rhodamine for the detection of surface-enhanced fluorescence, while, for the detection via Raman spectroscopy, streptavidin labeled with peroxidase was used and the signal was obtained after the application of 3,3',5,5'-tetramethylbenzidine (TMB) precipitating substrate. It was found that the substrate with the silver dendrites provided higher fluorescence signal intensity compared to the substrate with the silver aggregates, while the opposite was observed for the Raman signal. Thus, the best substrate was used for each detection method. A detection limit of 12.5 pg/mL was achieved with both detection approaches along with a linear dynamic range up to 500 pg/mL, enabling survivin determination in human serum samples from both healthy and ovarian cancer patients for cancer diagnosis and monitoring purposes.

Improved decision-making through life event prediction: A case study in the financial services industry

Life event prediction is an important tool for customer relationship management (CRM), because life events shift customers’ preferences towards different products and services. Existing life event research mainly uses cross-sectional data, whereas in the CRM field, incorporating longitudinal data is increasingly common. Because longitudinal data can capture the dynamics of customer behavior, opportunities arise to benchmark the power of longitudinal customer data for predictions of cross-sectional versus longitudinal life events. Therefore, this study compares statistical and machine learning (SaML) classifiers, such as logistic regression, random forest, and XGBoost, with long- and short-term memory networks (LSTM), using data represented in both cross-sectional and longitudinal setups for life event prediction. Through a real-life longitudinal customer data set from a European bank, the authors represent the longitudinal data in a cross-sectional data format, using featurization in the form of aggregation. The available data cover 42 end-of-month snapshots for 760,438 unique customers. For marketing decision-making literature, this article (1) introduces three novel life events (i.e., primary, secondary, and rental residence purchases) to life event predictions; (2) offers guidance for how to leverage longitudinal customer data, according to the comparison of various featurization approaches and benchmarking SaML classifiers against LSTM; and (3) clarifies the importance of features and timing for improving marketing decision-making dynamically. The results show that aggregating features over time is preferable as a featurization approach for cross-sectional modeling using SaML classifiers. Furthermore, LSTM can capture behavioral changes over time, unlike SaML classifiers. It also performs significantly better than SaML classifiers on the area under curve and F1 metrics. Insights into the uses of integrated gradients reveal that feature importance changes over time. An integrated gradients method can assist decision-makers in their efforts to plan effective communication with customers in advance, such as by allocating more resources to customers who exhibit high probabilities of a particular life event occurrence.

Aggregation Behavior of CHR-bis(BODIPY) Bichromophores in THF-water Mixtures: Effect of Linking Positions and Aryl-spacer Substituents.

Aggregation-caused quenching effect (ACQ) greatly limits the practical use of many organic luminophores in biomedicine, optics and electronics. The comparative analysis of aggregation characteristics of CHR-bis(BODIPY) bichromophores 1-6 with R = H, Ph, MeOPh and various linking positions (α,α-; α,β-; β,β- and β',β'-) in THF-water mixtures with different water fractions or dye concentrations is first presented in this article. Both the linking style 1-4 and the arylation of the spacer with phenyl (Ph-) 5 or methoxyphenyl (MeOPh-) 6 substituents strongly affect the formation of luminophore aggregated forms in binary THF-water mixtures. The α,α-and β,β-isomers (1 and 3) form non-fluorescent H-type aggregates in THF-water mixtures with fw > 70%. The α,β-; β',β'-isomers (2, 4) and the MeOPh-substituted β,β-bichromophore 6 are characterized by predominant formation fluorescent aggregates. All bichromophores are characterized by the presence of residual amounts of non-aggregated forms in binary mixtures with maximum water content. The results are useful for controlling the aggregation behavior and spectral characteristics of CHR-bis(BODIPY) bichromophores in aqueous-organic media, which is important in the development of biomarkers and PDT agents.

A Zero Auxiliary Knowledge Membership Inference Attack on Aggregate Location Data

Location data is frequently collected from populations and shared in aggregate form to guide policy and decision making. However, the prevalence of aggregated data also raises the privacy concern of membership inference attacks (MIAs). MIAs infer whether an individual's data contributed to the aggregate release. Although effective MIAs have been developed for aggregate location data, these require access to an extensive auxiliary dataset of individual traces over the same locations, which are collected from a similar population. This assumption is often impractical given common privacy practices surrounding location data. To measure the risk of an MIA performed by a realistic adversary, we develop the first Zero Auxiliary Knowledge (ZK) MIA on aggregate location data, which eliminates the need for an auxiliary dataset of real individual traces. Instead, we develop a novel synthetic approach, such that suitable synthetic traces are generated from the released aggregate. We also develop methods to correct for bias and noise, to show that our synthetic-based attack is still applicable when privacy mechanisms are applied prior to release. Using two large-scale location datasets, we demonstrate that our ZK MIA matches the state-of-the-art Knock-Knock (KK) MIA across a wide range of settings, including popular implementations of differential privacy (DP) and suppression of small counts. Furthermore, we show that ZK MIA remains highly effective even when the adversary only knows a small fraction (10%) of their target's location history. This demonstrates that effective MIAs can be performed by realistic adversaries, highlighting the need for strong DP protection.

A simple model linking radiative–convective instability, convective aggregation and large-scale dynamics

Abstract. A simple model is presented which is designed to analyse the relation between the phenomenon of convective aggregation at small scales and larger-scale variability that results from coupling between dynamics and moisture in the tropical atmosphere. The model is based on single-layer dynamical equations coupled to a moisture equation to represent the dynamical effects of latent heating and radiative heating. The moisture variable q evolves through the effect of horizontal convergence, nonlinear horizontal advection and diffusion. Following previous work, the coupling between moisture and dynamics is included in such a way that a horizontally homogeneous state may be unstable to inhomogeneous disturbances, and, as a result, localised regions evolve towards either dry or moist states, with divergence or convergence respectively in the horizontal flow. The time evolution of the spatial structure of the dry and moist regions is investigated using a combination of theory and numerical simulation. One aspect of the evolution is a spatial coarsening that, if moist regions and dry regions are interpreted as convecting and non-convecting respectively, represents a form of convective aggregation. When the weak temperature gradient (WTG) approximation (i.e. a local balance between heating and convergence) applies, and horizontal advection is neglected, the system reduces to a nonlinear reaction–diffusion equation for q, and the coarsening is a well-known aspect of such systems. When nonlinear advection of moisture is included, the large-scale flow that arises from the spatial pattern of divergence and convergence leads to a distinctly different coarsening process. When thermal and frictional damping and f-plane rotation are included in the dynamics, there is a dynamical length scale Ldyn that sets an upper limit for the spatial coarsening of the moist and dry regions. The f-plane results provide a basis for interpreting the behaviour of the system on an equatorial β plane, where the dynamics implies a displacement in the zonal direction of the divergence relative to q and hence to coherent equatorially confined zonally propagating disturbances, comprising separate moist and dry regions. In many cases the propagation speed and direction depend on the equatorial wave response to the moist heating, with the relative strength of the Rossby wave response to the Kelvin wave response determining whether the propagation is eastward or westward. Within this model, the key overall properties of the propagating disturbances, the spatial scale and the phase speed, depend on nonlinearity in the coupling between moisture and dynamics, and any linear theory for such disturbances therefore has limited usefulness. The model described here, in which the moisture and dynamical fields vary in two spatial dimensions and important aspects of nonlinearity are captured, provides an intermediate model between theoretical models based on linearisation and one spatial dimension and general circulation models (GCMs) or convection-resolving models.

Prion protein pathology in Ubiquilin 2 models of ALS

Mutations in UBQLN2 cause ALS and frontotemporal dementia (FTD). The pathological signature in UBQLN2 cases is deposition of highly unusual types of inclusions in the brain and spinal cord that stain positive for UBQLN2. However, what role these inclusions play in pathogenesis remains unclear. Here we show cellular prion protein (PrPC) is found in UBQLN2 inclusions in both mouse and human neuronal induced pluripotent (IPSC) models of UBQLN2 mutations, evidenced by the presence of aggregated forms of PrPC with UBQLN2 inclusions. Turnover studies indicated that the P497H UBQLN2 mutation slows PrPC protein degradation and leads to mislocalization of PrPC in the cytoplasm. Immunoprecipitation studies indicated UBQLN2 and PrPC bind together in a complex. The abnormalities in PrPC caused by UBQLN2 mutations may be relevant in disease pathogenesis.

Oleuropein enhances proteasomal activity and reduces mutant huntingtin-induced cytotoxicity.

Huntington's disease (HD) is a hereditary neurodegenerative disorder that primarily affects the striatum, a brain region responsible for movement control. The disease is characterized by the mutant huntingtin (mHtt) proteins with an extended polyQ stretch, which are prone to aggregation. These mHtt aggregates accumulate in neurons and are the primary cause of the neuropathology associated with HD. To date, no effective cure for HD has been developed. The immortalized STHdh Q111/Q111 striatal cell line, the mHtt-transfected wild-type STHdh Q7/Q7 striatal cell line, and N2a cells were used as Huntington's disease cell models. Flow cytometry was used to assess cellular reactive oxygen species and transfection efficiency. The CCK-8 assay was used to measure cell viability, while fluorescence microscopy was used to quantify aggregates. Immunoblotting analyses were used to evaluate the effects on protein expression. Polyphenols are natural antioxidants that offer neuroprotection in neurological disorders. In this study, we provide evidence that oleuropein, the primary polyphenol in olive leaves and olive oil, enhances cell viability in HD cell models, including. STHdh Q7/Q7 STHdh Q7/Q7 striatal cells, N2a cells ectopically expressing the truncated mHtt, and STHdh Q111/Q111 striatal cells expressing the full-length mHtt. Oleuropein effectively reduced both soluble and aggregated forms of mHtt protein in these HD model cells. Notably, the reduction of mHtt aggregates associated with oleuropein was linked to increased proteasome activity rather than changes in autophagic flux. Oleuropein seems to modulate proteasome activity through an unidentified pathway, as it did not affect the 20S proteasome catalytic β subunits, the proteasome regulator PA28γ, or multiple MAPK pathways. We demonstrated that oleuropein enhances the degradation of mHtt by increasing proteasomal protease activities and alleviates mHtt-induced cytotoxicity. Hence, we propose that oleuropein and potentially other polyphenols hold promise as a candidate for alleviating Huntington's disease.