Search Results (42)

Background: Despite effective antiretroviral therapy, HIV-associated neurocognitive disorders (HANDs) remain prevalent, highlighting the need for sensitive biomarkers of early brain alterations. Trace-weighted diffusion spectroscopic imaging offers a non-invasive means to assess microstructural changes in brain metabolites in a single shot by measuring apparent diffusion coefficients (ADCs) of total N-acetylaspartate (tNAA), total creatine (tCr), total choline (tCho), and water. Methods: In this study, we used trace-weighted single-shot diffusion-weighted radial echo-planar spectroscopic imaging (DW-RESPI) to investigate metabolite diffusion and relative concentrations in the brains of people living with HIV (PLWH). Using a 3T MRI scanner, we studied 16 PLWH and 15 healthy controls (HCs), and we collected two sets of data with low and high b-values from which metabolite ADCs were computed. Metabolite ratios were derived from the low b-value spectra. A brief neuropsychological assessment evaluated attention, executive function, and memory in a subset of subjects. Cognitive and affective performance was quantified using domain-specific deficit scores, as well as depression and anxiety assessments, offering a comprehensive evaluation of neurobehavioral function. In the male subgroup (N = 15) of PLWH, we calculated the correlations between ADC values and neuropsychological domain scores. Results: tNAA, tCr, tCho, and water ADC values were significantly elevated in multiple gray and white matter regions in PLWH compared to HC, with the most pronounced differences observed in the superior precuneus, anterior cingulate cortex, and corona radiata. Notably, regional ADC values and metabolite ratios showed significant correlations with neuropsychological domain scores. Conclusions: These findings indicate the potential of metabolite and water diffusion metrics as biomarkers for HIV-associated microstructural brain alterations and cognitive impairment. However, the small sample size and preliminary nature of this data warrant further investigation to validate these findings. Full article

A novel S = 1/2 paramagnetic chelating ligand tert-butyl 5-(p-biphenylyl)-2-pyridyl nitroxide (bppyNO) and its S = 1 nickel(II) ion complex [Ni(bppyNO)₂Br₂] were synthesized. X-ray crystallography revealed a 2p–3d–2p heterospin triad, with half of the molecule being crystallographically independent. A relatively planar chelate geometry with the torsion angle ϕ(Ni-O-N-C_2py) = −10.6(5)° at 300 K becomes significantly out-of-plane distorted with ϕ = −46.9(8) and 26.1(11)° at 90 K accompanied by disorder at the oxygen site. The torsion angle changes, Δϕ = 36° and 37°, are among the largest reported for related compounds. Magnetic measurements indicate gradual and incomplete spin transition-like behavior around 143(2) K. A three-state model involving an intermediate-spin (S_total = 1) state is proposed to explain non-zero χ_mT plateau in a low-temperature region. Density functional theory calculations using the determined structures support the proposed mechanism. Furthermore, geometry optimizations assuming S_total = 0, 1, and 2 are in good agreement with the present model. Full article

Cholesterol plays an essential role in biological membranes and is crucial for maintaining their stability and functionality. In addition to biological membranes, cholesterol is also used in various synthetic lipid-based structures such as liposomes, proteoliposomes, and nanodiscs. Cholesterol regulates membrane properties by influencing the density of lipids, phase separation into liquid-ordered (Lo) and liquid-disordered (Ld) areas, and stability of protein–membrane interactions. For planar bilayers, cholesterol thickens the membrane, decreases permeability, and brings lipids into well-ordered domains, thereby increasing membrane rigidity by condensing lipid packing, while maintaining lateral lipid mobility in disordered regions to preserve overall membrane fluidity. It modulates membrane curvature in curved bilayers and vesicles, and stabilizes low-curvature regions, which are important for structural integrity. In liposomes, cholesterol facilitates drug encapsulation and release by controlling bilayer flexibility and stability. In nanodiscs, cholesterol enhances structural integrity and protein compatibility, which enables the investigation of protein–lipid interactions under physiological conditions. In proteoliposomes, cholesterol regulates the conformational stability of embedded proteins that have implications for protein–lipid interaction. Developments in molecular dynamics (MD) techniques, from coarse-grained to all-atom simulations, have shown how cholesterol modulates lipid tail ordering, membrane curvature, and flip-flop behavior in response to concentration. Such simulations provide insights into the mechanisms underlying membrane-associated diseases, aiding in the design of efficient drug delivery systems. In this review, we combine results from MD simulations to provide a synoptic explanation of cholesterol’s complex function in regulating membrane behavior. This synthesis combines fundamental biophysical information with practical membrane engineering, underscoring cholesterol’s important role in membrane structure, dynamics, and performance, and paving the way for rational design of stable and functional lipid-based systems to be used in medicine. In this review, we gather evidence from MD simulations to provide an overview of cholesterol’s complex function regulating membrane behavior. This synthesis connects the fundamental biophysical science with practical membrane engineering, which highlights cholesterol’s important role in membrane structure, dynamics, and function and helps us rationally design stable and functional lipid-based systems for therapeutic purposes. Full article

Cerebral organoids derived from human induced pluripotent stem cells (iPSCs) have emerged as powerful in vitro models for studying human brain development and neurological disorders. Understanding the electrophysiological properties of these organoids is crucial for evaluating their functional maturity and potential applications. However, the differentiation and maturation of stem cells into cerebral organoids is a long, slow, and error-prone process. Hence, it is vitally crucial to establish a non-invasive method of monitoring the process over a long period of time. In this study, a planar microelectrode array (MEA) with platinum (Pt) black electroplating is designed to monitor the electrophysiological activities and pharmacological responses of cerebral organoids using an external neural signal acquisition system interfaced with the MEA. The planar MEA with Pt black electroplating has a significantly reduced electrode impedance and exhibits a robust capability for the real-time detection of spontaneous neural activities, including extracellular spikes and local field potentials. Distinct electrophysiological signal strengths in cerebral organoids were observed at early and late developmental stages. Further pharmacological stimulations showed that 30 mM KCl would induce a marked increase in spike rate, indicating an enhancement of neuronal depolarization and an elevation of network excitability. This robust response to KCl stimulation in mature networks serves as a reliable indicator of neural maturity in cerebral organoids and underscores the platform’s potential for drug screening applications. This work highlights the integration of MEA technology with cerebral organoids, offering a powerful platform for real-time electrophysiological monitoring. It provides new insights into the functional maturation of neural networks and establishes a reliable system for drug screening and disease modeling, facilitating future research into human brain physiology and pathology. Full article

The ternary Zintl phase, Yb₂CdSb₂, was discovered to exist in two different polymorphic forms. In addition to the orthorhombic α-Yb₂CdSb₂ (space group Cmc2₁) known for its excellent thermoelectric properties, we present the synthesis and characterization of the crystal and electronic structure of its monoclinic variant, β-Yb₂CdSb₂. Structural characterization was performed with the single-crystal X-ray diffraction method. β-Yb₂CdSb₂ crystallizes in a monoclinic crystal system with the non-centrosymmetric space group Cm (Z = 33, a = 81.801(5) Å, b = 4.6186(3) Å, c = 12.6742(7) Å, β = 93.0610(10)°) and constitutes a new structure type. The complex crystal structure of β-Yb₂CdSb₂ contrasts with the previously studied β-Ca₂CdPn₂ (Pn = P, As, Sb) polymorphs, although it shares similar structural features. It consists of three different layers, made of corner-sharing [CdSb₄] tetrahedra and stacked in the ABC sequence. The layers are interconnected via [CdSb₃] trigonal planar units. Multiple Yb and Cd atomic sites exhibit partial occupancy, resulting in extensive structural disorder. Valence electron partitioning within the Zintl–Klemm formalism yields the formulation (Yb²⁺)_1.98(Cd²⁺)_1.01(Sb³⁻)₂(h⁺)_0.02, highlighting the nearly charge-balanced composition. Detailed electronic structure calculations reveal the closed band gap and presumably semimetallic nature of β-Yb₂CdSb₂ with the band structure features hinting at potential topological properties. Full article

DNA is fundamental for storing and transmitting genetic information. Analyzing DNA or RNA base sequences enables the identification of genetic disorders, monitoring gene expression, and detecting pathogens. Traditional detection techniques like polymerase chain reaction (PCR) and next-generation sequencing (NGS) have limitations, including complexity, high cost, and the need for advanced computational skills. Therefore, there is a significant demand for enzyme-free and amplification-free strategies for rapid, low-cost, and sensitive DNA detection. DNA biosensors, especially those utilizing plasmonic nanomaterials, offer a promising solution. This study introduces a novel DNA-functionalized waveguide-enhanced nanoplasmonic optofluidic biosensor using a nanogold-linked sorbent assay for enzyme-free and amplification-free DNA detection. Integrating plasmonic gold nanoparticles (AuNPs) with a glass planar waveguide (WG) and a microfluidic channel, fabricated through cost-effective, vacuum-free methods, the biosensor achieves specific detection of complementary target DNA sequences. Utilizing a sandwich architecture, AuNPs labeled with detection DNA probes enhance sensitivity by altering evanescent wave distribution and inducing plasmon resonance modes. The biosensor demonstrated exceptional performance in DNA detection, achieving a limit of detection (LOD) of 33.1 fg/mL (4.36 fM) with a rapid response time of approximately 8 min. This ultrasensitive, rapid, and cost-effective biosensor exhibits minimal background nonspecific adsorption, making it highly suitable for clinical applications and early disease diagnosis. The innovative design and fabrication processes offer significant advantages for mass production, presenting a viable tool for precise disease diagnostics and improved clinical outcomes. Full article

Conjugated polymers (CPs) are widely used as conductive materials in various applications, with their conductive properties adjustable through chemical doping. While doping enhances the thermoelectric properties of CPs due to improved main-chain transport, overdoping can distort the polymer structure, increasing energy disorder and impeding intrinsic electrical transport. This study explored how different dopants affect the structural integrity and electrical transport properties of CPs. We found that dopants vary in their impact on CP structure, consequently altering their electrical transport capabilities. Specifically, ferric chloride (FeCl₃)-doped indacenodithiophene-co-benzothiadiazole (IDTBT) shows superior electrical transport properties to triethyloxonium hexachloroantimonate (OA)-doped IDTBT due to enhanced backbone planarity and rigidity, which facilitate carrier transport and lower energetic disorder. These results highlight the critical role of dopant selection in optimizing CPs for advanced applications, suggesting that strategic dopant choices can significantly refine the charge transport characteristics of CPs, paving the way for their industrialization. Full article

Background: Myotonic dystrophy type 1 (DM1) is a rare multisystemic genetic disorder with motor hallmarks of myotonia, muscle weakness and wasting. DM1 patients have an increased risk of falling of multifactorial origin, and proprioceptive and vestibular deficits can contribute to this risk. Abnormalities of muscle spindles in DM1 have been known for years. This observational cross-sectional study was based on the hypothesis of impaired cervical proprioception caused by alterations in the neck spindles. Methods: Head position sense was measured in 16 DM1 patients and 16 age- and gender-matched controls. A head-to-target repositioning test was requested from blindfolded participants. Their head was passively rotated approximately 30° leftward or rightward and flexed or extended approximately 25°. Participants had to replicate the imposed positions. An optoelectronic system was adopted to measure the angular differences between the reproduced and the imposed positions (joint position error, JPE, °) concerning the intended (sagittal, horizontal) and unintended (including the frontal) planar projections. In DM1 patients, JPEs were correlated with clinical and balance measures. Static balance in DM1 patients was assessed through dynamic posturography. Results: The accuracy and precision of head repositioning in the intended sagittal and horizontal error components did not differ between DM1 and controls. On the contrary, DM1 patients showed unintended side-bending to the left and the right: the mean [95%CI] of frontal JPE was −1.29° [−1.99°, −0.60°] for left rotation and 0.98° [0.28°, 1.67°] for right rotation. The frontal JPE of controls did not differ significantly from 0° (left rotation: 0.17° [−0.53°, 0.87°]; right rotation: −0.22° [−0.91°, 0.48°]). Frontal JPE differed between left and right rotation trials (p < 0.001) only in DM1 patients. No correlation was found between JPEs and measures from dynamic posturography and clinical scales. Conclusions: Lateral head bending associated with head rotation may reflect a latent impairment of neck proprioception in DM1 patients. Full article

We present a new combinatorial approach to the Ising model incorporating arbitrary bond weights on planar graphs. In contrast to existing methodologies, the exact free energy is expressed as the determinant of a set of ordered and disordered operators defined on a planar graph and the corresponding dual graph, respectively, thereby explicitly demonstrating the Kramers–Wannier duality. The implications of our derived formula for the Random-Bond Ising Model are further elucidated. Full article

Eyespot foci on butterfly wings function as organizers of eyespot color patterns during development. Despite their importance, focal structures have not been examined in detail. Here, we microscopically examined scales, sockets, and the wing membrane in the butterfly eyespot foci of both expanded and unexpanded wings using the Blue Pansy butterfly Junonia orithya. Images from a high-resolution light microscope revealed that, although not always, eyespot foci had scales with disordered planar polarity. Scanning electron microscopy (SEM) images after scale removal revealed that the sockets were irregularly positioned and that the wing membrane was physically distorted as if the focal site were mechanically squeezed from the surroundings. Focal areas without eyespots also had socket array irregularities, but less frequently and less severely. Physical damage in the background area induced ectopic patterns with socket array irregularities and wing membrane distortions, similar to natural eyespot foci. These results suggest that either the process of determining an eyespot focus or the function of an eyespot organizer may be associated with wing-wide mechanics that physically disrupt socket cells, scale cells, and the wing membrane, supporting the physical distortion hypothesis of the induction model for color pattern determination in butterfly wings. Full article

The planar cell polarity (PCP) system is essential for positioning cells in 3D networks to establish the proper morphogenesis, structure, and function of organs during embryonic development. The PCP system uses inter- and intracellular feedback interactions between components of the core PCP, characterized by coordinated planar polarization and asymmetric distribution of cell populations inside the cells. PCP signaling connects the anterior–posterior to left–right embryonic plane polarity through the polarization of cilia in the Kupffer’s vesicle/node in vertebrates. Experimental investigations on various genetic ablation-based models demonstrated the functions of PCP in planar polarization and associated genetic disorders. This review paper aims to provide a comprehensive overview of PCP signaling history, core components of the PCP signaling pathway, molecular mechanisms underlying PCP signaling, interactions with other signaling pathways, and the role of PCP in organ and embryonic development. Moreover, we will delve into the negative feedback regulation of PCP to maintain polarity, human genetic disorders associated with PCP defects, as well as challenges associated with PCP. Full article

The calcium ion (Ca²⁺) has been linked to type 2 diabetes mellitus (T2DM), although the role of Ca²⁺ in this disorder is the subject of intense investigation. Serum Ca²⁺ dyshomeostasis is associated with the development of insulin resistance, reduced insulin sensitivity, and impaired glucose tolerance. However, the molecular mechanisms involving Ca²⁺ ions in pancreatic β-cell loss and subsequently in T2DM remain poorly understood. Implicated in the decline in β-cell functions are aggregates of human islet amyloid polypeptide (hIAPP), a small peptide secreted by β-cells that shows a strong tendency to self-aggregate into β-sheet-rich aggregates that evolve toward the formation of amyloid deposits and mature fibrils. The soluble oligomers of hIAPP can permeabilize the cell membrane by interacting with bilayer lipids. Our study aimed to evaluate the effect of Ca²⁺ on the ability of the peptide to incorporate and form ion channels in zwitterionic planar lipid membranes (PLMs) composed of palmitoyl-oleoyl-phosphatidylcholine (POPC) and on the aggregation process of hIAPP molecules in solution. Our results may help to clarify the link between Ca²⁺ ions, hIAPP peptide, and consequently the pathophysiology of T2DM. Full article

Autism spectrum disorder (ASD) necessitates prompt diagnostic scrutiny to enable immediate, targeted interventions. This study unveils an advanced convolutional-neural-network (CNN) algorithm that was meticulously engineered to examine resting-state functional magnetic resonance imaging (fMRI) for early ASD detection in pediatric cohorts. The CNN architecture amalgamates convolutional, pooling, batch-normalization, dropout, and fully connected layers, optimized for high-dimensional data interpretation. Rigorous preprocessing yielded 22,176 two-dimensional echo planar samples from 126 subjects (56 ASD, 70 controls) who were sourced from the Autism Brain Imaging Data Exchange (ABIDE I) repository. The model, trained on 17,740 samples across 50 epochs, demonstrated unparalleled diagnostic metrics—accuracy of 99.39%, recall of 98.80%, precision of 99.85%, and an F1 score of 99.32%—and thereby eclipsed extant computational methodologies. Feature map analyses substantiated the model’s hierarchical feature extraction capabilities. This research elucidates a deep learning framework for computer-assisted ASD screening via fMRI, with transformative implications for early diagnosis and intervention. Full article

The antimicrobial peptide Smp24, originally derived from the venom of Scorpio maurus palmatus, is a promising candidate for further drug development. However, before doing so, greater insight into the mechanism of action is needed to construct a reliable structure–activity relationship. The aim of this study was to specifically investigate the critical early stages of peptide-induced membrane disruption. Single-channel current traces were obtained via planar patch-clamp electrophysiology, with multiple types of pore-forming events observed, unlike those expected from the traditional, more rigid mechanistic models. To better understand the molecular-level structures of the peptide-pore assemblies underlying these observed conductance events, molecular dynamics simulations were used to investigate the peptide structure and orientation both before and during pore formation. The transition of the peptides to transmembrane-like states within disordered toroidal pores occurred due to a peptide-induced bilayer-leaflet asymmetry, explaining why pore stabilization does not always follow pore nucleation in the experimental observations. To fully grasp the structure–activity relationship of antimicrobial peptides, a more nuanced view of the complex and dynamic mechanistic behaviour must be adopted. Full article

The global issue of pollution caused by endocrine-disrupting chemicals (EDCs) has been gaining increasing attention. Among the EDCs of environmental concern, 17β-estradiol (E2) can produce the strongest estrogenic effects when it enters the organism exogenously through various routes and has the potential to cause harm, including malfunctions of the endocrine system and development of growth and reproductive disorders in humans and animals. Additionally, in humans, supraphysiological levels of E2 have been associated with a range of E2-dependent disorders and cancers. To ensure environmental safety and prevent potential risks of E2 to human and animal health, it is crucial to develop rapid, sensitive, low cost and simple approaches for detecting E2 contamination in the environment. A planar microwave sensor for E2 sensing is presented based on the integration of a microstrip transmission line (TL) loaded with a Peano fractal geometry with a narrow slot complementary split-ring resonator (PF-NSCSRR) and a microfluidic channel. The proposed technique offers a wide linear range for detecting E2, ranging from 0.001 to 10 mM, and can achieve high sensitivity with small sample volumes and simple operation methods. The proposed microwave sensor was validated through simulations and empirical measurements within a frequency range of 0.5–3.5 GHz. The E2 solution was delivered to the sensitive area of the sensor device via a microfluidic polydimethylsiloxane (PDMS) channel with an area of 2.7 mm² and sample value of 1.37 µL and measured by a proposed sensor. The injection of E2 into the channel resulted in changes in the transmission coefficient (S₂₁) and resonance frequency (F_r), which can be used as an indicator of E₂ levels in solution. The maximum quality factor of 114.89 and the maximum sensitivity based on S₂₁ and F_r at a concentration of 0.01 mM were 1746.98 dB/mM and 40 GHz/mM, respectively. Upon comparing the proposed sensor with the original Peano fractal geometry with complementary split-ring (PF-CSRR) sensors without a narrow slot, several parameters were evaluated, including sensitivity, quality factor, operating frequency, active area, and sample volume. The results showed that the proposed sensor exhibited an increased sensitivity of 6.08% and had a 40.72% higher quality factor, while the operating frequency, active area, and sample volume showed decreases of 1.71%, 25%, and 28.27%, respectively. The materials under tests (MUTs) were analyzed and categorized into groups using principal component analysis (PCA) with a K-mean clustering algorithm. The proposed E2 sensor has a compact size and simple structure that can be easily fabricated with low-cost materials. With the small sample volume requirement, fast measurement with a wide dynamic range, and a simple protocol, this proposed sensor can also be applied to measure high E2 levels in environmental, human, and animal samples. Full article