Khushboo Singh, Roon Banerjee, Chandrakanta Potdar
et al.
Mutations in leucine-rich repeat kinase 2 (LRRK2) are among the most common genetic causes of Parkinson’s disease (PD), yet substantial heterogeneity exists among pathogenic variants. How mutations in distinct functional domains of LRRK2 differentially perturb cellular homeostasis remains incompletely understood. Here, we compared two pathogenic LRRK2 mutations—G2019S in the kinase domain and I1371V in the GTPase domain—across multiple cellular models, including SH-SY5Y and U87 cells, and healthy human iPSC-derived floor plate cells. We demonstrate that the I1371V mutation induces markedly more severe cellular dysfunction than G2019S. I1371V-expressing cells exhibited elevated LRRK2 autophosphorylation at S1292 and robust hyperphosphorylation of Rab8A and Rab10, indicating enhanced downstream signaling. These alterations impaired sterol trafficking, leading to selective depletion of membrane cholesterol without changes in total cellular cholesterol. Consequently, I1371V cells displayed increased membrane fluidity, disrupted microdomain organization, altered membrane topology, reduced caveolin-1 expression, and impaired dopamine transporter surface expression and dopamine uptake. Lipidomic profiling further revealed a broad disruption of lipid homeostasis, including reductions in cholesteryl esters, sterols, sphingolipids, and glycerophospholipids, whereas G2019S cells showed comparatively modest changes. Pharmacological intervention revealed mutation-specific responses, with the non-selective LRRK2 modulator GW5074 outperforming the kinase-selective inhibitor MLi-2 in restoring Rab8A phosphorylation, membrane integrity, and dopaminergic function. Collectively, these findings identify membrane lipid dysregulation as a central cell biological mechanism in LRRK2-associated PD and underscore the importance of variant-specific therapeutic strategies.
McLuret, S. Joe Patrick Gnanaraj, Vanthana Jeyasingh
This study focuses on optimizing IoT-enabled stepped basin solar stills by integrating the Taguchi method, Particle Swarm Optimization (PSO), and Artificial Bee Colony (ABC) algorithms. The objective was to enhance distillate yield, thermal efficiency, and system performance by optimizing key parameters—water depth, basin material, phase change material (PCM) type, and reflector angle. The Taguchi orthogonal array minimized experimental runs, while PSO and ABC algorithms refined parameter selection. Experimental results showed that a combination of 5 mm water depth, black copper basin, salt hydrate PCM, and a 45° internal reflector angle achieved a distillate yield of 3200 ml/day with 78.05 % efficiency, nearing the theoretical maximum of 4100 ml/day. Real-time IoT monitoring enabled dynamic adjustments, further improving efficiency. The findings highlight the effectiveness of combining smart monitoring and advanced optimization techniques to create scalable and sustainable solar desalination solutions for water-scarce regions.
Koneru Suvarna Vani, Puppala Praneeth, Vivek Kommareddy
et al.
Human vision depends heavily on retinal tissue. The loss of eyesight may result from infections of the retinal tissues that are treated slowly or do not work at all. Additionally, the diagnosis is susceptible to inaccuracies when a large dataset is involved. Therefore, a fully automated transfer learning approach for diagnosing diabetic retinopathy (DR) is suggested to minimize human intervention while maintaining high classification accuracy. To address this issue, we proposed a transfer learning-based trilateral attention network (TaNet) for the classification. To boost the visual quality of the DR pictures, a contrast constrained adaptive histogram equalization approach is applied. The pre-processed pictures are then segmented using a bilateral segmentation network (BiSeNet). The BiSeNet segmented the optic disc and blood vessels individually. After the completion of segmentation, the features are extracted. Feature extraction is based on the wavelet scattering transformation approach. The results of many trials were evaluated against the Messidor-2, EYEPACS, and APTOS 2019 datasets. The proposed model was created using a refined pre-trained technique and transfer learning methodology. Finally, the suggested framework was tested using efficiency assessment methods, and the classification rate was recorded as having above 98% sensitivity, specificity, precision, and accuracy. The proposed approach yields greater performance and shows enhancement towards the existing approach.
Mulata Haile Nega, Derbew Fikadu Berhe, Vera Ribeiro
Abstract Background Statin-induced myopathy is reported to be associated with the solute carrier organic anion transporter family member 1B1 gene single nucleotide polymorphism, c.521 T > C. There is no epidemiologic data on this gene polymorphism in several countries. Therefore, this study aimed at assessing the genotype and allele frequencies of the gene variant in three countries. Methods This study involved healthy individuals from Colombia, Mozambique, and Portugal. Genomic DNA was isolated from blood samples using the Qiamp DNA Extraction Kit (Qiagen). The isolated DNA was genotyped using novel Polymerase Chain Reaction—Restriction Fragment Length Polymorphism. Microstat and GraphPad QuickCal software were used for the Chi-square test and the evaluation of Hardy–Weinberg equilibrium respectively. Results A total of 181 individuals’ blood samples were analyzed. Overall, the TT (74.0%) genotype was the highest and the CC (7.8%) was the lowest. Country wise genotypic frequencies were Colombia 47(70.2%) TT, 12(17.9%) TC and 8(11.9%) CC; Mozambique 47(88.7%) TT, 5(9.4%) TC, and 1(1.9%) CC; and Portugal 40(65.6%) TT, 16(26.2%) TC, and 5(8.2%) CC. The reference (T) allele was highest among Mozambicans (93.4%) compared to Colombians (79.1%) and Portuguese (78.7%). Mozambicans showed statistically significant genotypic and allelic frequency differences compared to Colombians (p < 0.01) and Portuguese (p < 0.01). Conclusions Overall and country-wise, CC genotype was less frequent and it is relatively high for Colombians and Portuguese populations. This finding may imply statins risk–benefit variability associated with CC genotype among these populations that needs further understanding.
Among mobile terrestrial animals, movement among microsites can allow individuals to behaviorally moderate their body temperatures and rates of water loss, which can have important consequences for activity times, growth, fecundity, and survival. Ground-layer vegetation can change the availability and variability of microclimates; however, gaps in our understanding of how individuals interact with the microclimates created by vegetation limit our ability to inform management actions for wildlife. Amphibians can simultaneously balance operant body temperatures and water loss and the availability of heterogeneous microclimates should moderate how effectively they are able to do so. However, relatively few studies have attempted to mechanistically demonstrate how ground vegetation-driven effects on microclimatic variation may affect amphibian performance and survival. Agent-based modeling (ABM) can incorporate behavior and other mechanisms to understand how animals interact with their environments to result in larger scale patterns. They are effective for exploring alternative scenarios and representing the uncertainty in systems. Here, we use ABMs to integrate field and laboratory measurements of movement behavior, physiology, and plant effects on near-ground microclimate to explore how ground vegetation and the availability of terrestrial refugia may affect the survival and terrestrial distributions of juvenile gopher frogs (Rana capito) under two weather regimes. We also examine how assumptions regarding micro-scale movement (< 1 m2) affect the influence of ground vegetation on survival and settlement within refugia. While all variables affected settlement and survival, our models predict that inter-annual variation in weather and the density and spatial distribution of permanent refugia likely have the greatest influence on juvenile survival. The benefit of increased ground vegetation was dependent on the reasonable assumption that gopher frogs exhibit microclimate habitat selection throughout the day and night to limit water loss. Our models suggest that vegetation would be most beneficial to amphibians under warmer weather regimes provided there is sufficient rainfall.
Deep learning technology has achieved breakthrough research results in the fields of medical computer vision and image processing. Generative adversarial networks (GANs) have demonstrated a capacity for image generation and expression ability. This paper proposes a new method called MWG-UNet (multiple tasking Wasserstein generative adversarial network U-shape network) as a lung field and heart segmentation model, which takes advantages of the attention mechanism to enhance the segmentation accuracy of the generator so as to improve the performance. In particular, the Dice similarity, precision, and F1 score of the proposed method outperform other models, reaching 95.28%, 96.41%, and 95.90%, respectively, and the specificity surpasses the sub-optimal models by 0.28%, 0.90%, 0.24%, and 0.90%. However, the value of the IoU is inferior to the optimal model by 0.69%. The results show the proposed method has considerable ability in lung field segmentation. Our multi-organ segmentation results for the heart achieve Dice similarity and IoU values of 71.16% and 74.56%. The segmentation results on lung fields achieve Dice similarity and IoU values of 85.18% and 81.36%.
Suraj Chakravarthi Raja, Won Suk You, Kian Jalaleddini
et al.
Tendon transfer surgery is often used to restore hand grasp function following high median-ulnar nerve palsy. This surgery typically reroutes and sutures the tendon of the extensor carpi radialis longus (ECRL) muscle to all four flexor digitorum profundus (FDP) tendons of the hand, coupling them together. This makes it difficult to grasp irregularly shaped objects. We propose inserting a novel implantable passive device between the FDP tendons to surgically construct a differential mechanism, enabling the fingers to individually adapt to the irregular contours during grasping. These passive implants with no moving parts are fabricated from biocompatible materials. We tested the implants’ ability to create differential flexion between the index and middle fingers when actuated by a single muscle in two human cadaver hands using a computerized closed-loop control paradigm. In these cadaveric models, the implants enabled significantly more differential flexion between the index and middle fingers for a wide range of donor tendon tensions. The implants also redistributed fingertip forces between fingers. When grasping uneven objects, the difference in contact forces between fingers reduced by nearly 23% compared to the current suture-based surgery. These results suggest that self-adaptive grasp is possible in tendon transfers that drive multiple distal flexor tendons.
Starting from a simple animal-biology example, a general, somewhat counter-intuitive property of diffusion random walks is presented. It is shown that for any (non-homogeneous) purely diffusing system, under any isotropic uniform incidence, the average length of trajectories through the system (the average length of the random walk trajectories from entry point to first exit point) is independent of the characteristics of the diffusion process and therefore depends only on the geometry of the system. This exact invariance property may be seen as a generalization to diffusion of the well-known mean-chord-length property (Case K. M. and Zweifel P. F., Linear Transport Theory (Addison-Wesley) 1967), leading to broad physics and biology applications.
Oscar O. Romero-Chapol, Abigail Varela-Pérez, Ana G. Castillo-Olmos
et al.
This study was aimed to prepare and characterize capsules loaded with <i>Lacticaseibacillus rhamnosus</i> GG (LGG), evaluating cell viability under gastrointestinal in vitro conditions and during storage in yogurt and apple juice, an alternative to traditional probiotic foods for people who are lactose intolerant. The capsules were prepared by ionic gelation, with an emulsification process as pretreatment. Cell viability of encapsulated LGG was evaluated after two different homogenization processes: magnetic stirring (AM) and Ultraturrax<sup>®</sup> homogenizer (UT). The system with the best relationship between viability and morphology was UT, which produced a viability of 85.80%. During in vitro evaluation, the capsules provided higher protection than free cells, up to 100% of cell viability. The morphology of capsules of both systems displayed a continuous and homogeneous surface. The cell viability of the encapsulated probiotics added in apple juice stored for 22 days at 4 °C was 86.16% for AM and 100% for UT, while the viability of free cells was 80.50%. In natural yogurt, the cell viability of the probiotics encapsulated stored 30 days at 4 °C was 100% for AM, 100% for UT, and 92.68% for free cells. This study suggests an alternative to preserve probiotic bacteria in a potential functional food.
Monocrystalline barium fluoride (BaF<sub>2</sub>) slab targets were irradiated by focused 46.9-nm laser radiation at various fluence levels above the ablation threshold. Well-developed ablation patterns with sharp edges were studied by AFM (atomic force microscopy). Their inner surfaces were uniformly covered by periodic structures. The spatial period of the ripples depends on the laser fluence. When the sample is rotated by 45°, the orientation of the grating-like structure changes accordingly. Thus, the grating vector of the periodic structure seems to be coupled to the crystallographic planes of the single crystal. This means that the XUV-laser induced ripples reported here differ from LIPSS (laser-induced periodic surface structures) associated with interference phenomena occurring on illuminated surfaces. Therefore, other mechanisms are discussed to explain the formation of the periodic nanostructures reported in this article.
Ian A Clark, Siawoosh Mohammadi, Martina F Callaghan
et al.
Conduction velocity is the speed at which electrical signals travel along axons and is a crucial determinant of neural communication. Inferences about conduction velocity can now be made in vivo in humans using a measure called the magnetic resonance (MR) g-ratio. This is the ratio of the inner axon diameter relative to that of the axon plus the myelin sheath that encases it. Here, in the first application to cognition, we found that variations in MR g-ratio, and by inference conduction velocity, of the parahippocampal cingulum bundle were associated with autobiographical memory recall ability in 217 healthy adults. This tract connects the hippocampus with a range of other brain areas. We further observed that the association seemed to be with inner axon diameter rather than myelin content. The extent to which neurites were coherently organised within the parahippocampal cingulum bundle was also linked with autobiographical memory recall ability. Moreover, these findings were specific to autobiographical memory recall and were not apparent for laboratory-based memory tests. Our results offer a new perspective on individual differences in autobiographical memory recall ability, highlighting the possible influence of specific white matter microstructure features on conduction velocity when recalling detailed memories of real-life past experiences.
Migratory soaring birds exhibit spatiotemporal variation in their circannual movements. Nevertheless, it remains uncertain how different winter environments affect the circannual movement patterns of migratory soaring birds. Here, we investigated annual movement strategies of American white pelicans <i>Pelecanus erythrorhynchos</i> (hereafter, pelican) from two geographically distinct wintering grounds in the Southern and Northern Gulf of Mexico (GOM). We hypothesized that hourly movement distance and home range size of a soaring bird would differ between different geographic regions because of different thermals and wind conditions and resource availability. We calculated average and maximum hourly movement distances and seasonal home ranges of GPS-tracking pelicans. We then evaluated the effects of hour of the day, seasons, two wintering regions in the Southern and Northern GOM, human footprint index, and relative pelican abundance from Christmas Bird Count data on pelican hourly movement distances and seasonal home ranges using linear mixed models and generalized linear mixed models. American white pelicans moved at greatest hourly distance near 1200 h at breeding grounds and during spring and autumn migrations. Both wintering populations in the Northern and Southern GOM exhibited similar hourly movement distances and seasonal home ranges at the shared breeding grounds and during spring and autumn migrations. However, pelicans wintering in the Southern GOM showed shorter hourly movement distances and smaller seasonal home ranges than those in the Northern GOM. Hourly movement distances and home ranges of pelicans increased with increasing human footprint index. Winter hourly movements and home ranges of pelicans differed between the Northern and Southern GOM; however, the winter difference in pelican movements did not carry over to the shared breeding grounds during summers. Therefore, exogenous factors may be the primary drivers to shape the flying patterns of migratory soaring birds.
Yayoi Aizawa, Atsushi Watanabe, Atsushi Watanabe
et al.
In recent years, genetic counseling has started playing a major role in the field of genomic medicine. There are currently about 7,000 genetic counselors in more than 28 countries, with 267 certified genetic counselors in Japan alone (about 2 per million population, as of April 2020). While the rapid advancement of genomic medicine has expanded this field, the challenges genetic counselors face are also evolving. This article aims to provide an overview of the institutional and social issues surrounding genetic counselors in Japan and discuss implications for the global community. In Japan, with the rapid changes in genomic medicine and the establishment of a delivery mechanism within the healthcare system, several issues need to be discussed. First, many genetic testing, counseling, and preventive healthcare programs are not covered by public health insurance. Second, reducing human resource shortages for genetic counseling is an urgent issue. Third, the lack of a national qualification in the profession is critically important issue in the field. Fourth, research on the role and value of genetic counselors is still limited. To address these issues, discussions among relevant stakeholders, including genetic counselors, professionals in genomic medicine, and lawmakers, are necessary. Additionally, we believe that research by genetic counselors to evaluate and improve their practice and examine institutional and social issues is crucial for developing their profession’s activities and delivering high-quality healthcare to many people. To establish the position and role of the relatively new profession of genetic counselor, sharing information and collaborating on institutional and social challenges faced by genetic counselors globally will be beneficial.
In the central nervous system, oligodendrocytes produce myelin sheaths that enwrap neuronal axons to provide trophic support and increase conduction velocity. New oligodendrocytes are produced throughout life through a process referred to as oligodendrogenesis. Oligodendrogenesis consists of three canonical stages: the oligodendrocyte precursor cell (OPC), the premyelinating oligodendrocyte (preOL), and the mature oligodendrocyte (OL). However, the generation of oligodendrocytes is inherently an inefficient process. Following precursor differentiation, a majority of premyelinating oligodendrocytes are lost, likely due to apoptosis. If premyelinating oligodendrocytes progress through this survival checkpoint, they generate new myelinating oligodendrocytes in a process we have termed integration. In this review, we will explore the intrinsic and extrinsic signaling pathways that influence preOL survival and integration by examining the intrinsic apoptotic pathways, metabolic demands, and the interactions between neurons, astrocytes, microglia, and premyelinating oligodendrocytes. Additionally, we will discuss similarities between the maturation of newly generated neurons and premyelinating oligodendrocytes. Finally, we will consider how increasing survival and integration of preOLs has the potential to increase remyelination in multiple sclerosis. Deepening our understanding of premyelinating oligodendrocyte biology may open the door for new treatments for demyelinating disease and will help paint a clearer picture of how new oligodendrocytes are produced throughout life to facilitate brain function.
Raheel Shahzad, Mohamed Ewas, Putri Widyanti Harlina
et al.
Abstract Background Elevated ultraviolet-B (UV-B) radiation is potentially deleterious to many organisms specifically crop plants and has become a global challenge. Rice is an exceptionally important staple food which is grown worldwide, and many efforts have been done recently to improve rice varieties against UV-B stress. This current study aims to investigate the effects of exogenous application of β-sitosterol (βSito) on growth improvement and tolerance level of rice plants against prolonged UV-B stress. The physiological and metabolic responses were evaluated in rice plants not supplemented with βSito (Nβ) and those supplemented with βSito (Sβ). Results The Nβ and Sβ plants were grown under non-stress (ns) and under prolonged UV-B stress (uvs) conditions and termed as Nβns, Sβns and Nβuvs, Sβuvs, respectively. The application of βSito contributes positively under non-stress and specifically to UV-B stress in terms of improving numerous physiological parameters associated with growth and development such as shoot and root length, RWC, whole plant biomass, chlorophyll pigments, and photosynthetic-related parameters (Pn, Gs, Tr, WUEi, Fv/Fm, and NPQ) in Sβ compared with Nβ plants. Moreover, enhanced oxidative stress tolerance of Sβuvs vs. Nβuvs plants under stress was attributed to low levels of ROS and substantial trigger in activities of antioxidant enzymes (SOD, POD, CAT, and APX). Metabolic analysis was performed using GC-TOFMS, which revealed higher accumulation of several key metabolites including organic acids, sugars, amino acids, and others in Sβuvs vs. Nβuvs plants, which were mainly reduced in Nβ plants under stress vs. non-stress conditions. Conclusion These results provide useful data regarding the important role of βSito on growth maintenance and modulation of several metabolites associated with osmotic and redox adjustments during UV-B stress tolerance in rice plants. Importantly, βSito-regulated plasticity could further be explored specifically in relation to different environmental stresses in other economically useful crop plants.
José J. Mbimbi Mayi Munene, Melanie L. J. Stiassny, Raoul J. C. Monsembula Iyaba
et al.
The ichthyofauna of the Lulua River, a large right bank tributary of the Kasai River in central Africa, is among the most poorly documented in the Kasai ecoregion. To remedy this lack of knowledge, sampling was carried out between 2007 and 2014 along the main channel and in many tributaries. A total of 201 species distributed in 81 genera, 24 families, and 12 orders are reported from the lower reaches of the Lulua. The species richness reported in this study represents a substantially improved documentation of the Lulua ichthyofauna (historically estimated at only 79 species). Here, 129 species are recorded for the first time, bringing the total number of known species to 208. Among these, five have recently been described: <i>Raiamas brachyrhabdotos</i> Katemo Manda, Snoeks, Choca Manda, and Vreven 2018, <i>Distichodus kasaiensis</i> Moelants, Snoeks, and Vreven, 2018, <i>Distichodus polli</i> Abwe, Snoeks, Choca Manda, and Vreven 2019, <i>Epiplatys atractus</i> Van Der Zee, Mbimbi, and Sonnenberg 2013, and <i>Hypsopanchax stiassnyae</i> Van Der Zee, Sonnenberg, and Mbimbi 2015; numerous additional taxa are currently under investigation. Recognized here as a continental hotspot of ichthyofaunal diversity, the Lulua is under extreme threat from exploitation of forest products for building materials, deforestation for shifting agriculture and charcoal exploitation, destructive fishing practices, and mining, all of which are rapidly increasing in the watershed. The present study provides baseline documentation for use in conservation planning and future developmental projects in the Kasai ecoregion in general and Lulua River basin in particular.
Abstract The investigation of genetic diversity in natural populations of species that show potential for use in reforestation programs is a key step in making management decisions. However, reforestation programs with native species in Brazil are still rarely based on a genetic understanding of the seed matrices used for seedling production. This is also the case for Myrsine umbellata, a dioecious shrub within the family Primulaceae that has been used in reforestation programs in Brazil, mainly due to its high production capacity of fruits attractive to the avifauna. The goal of this study was to measure intra- and interpopulational genetic diversity in natural populations of M. umbellata in six forest remnants of the Atlantic Forest using ISSR markers. The results revealed that the intrapopulational genetic diversity was greater than the genetic diversity among the studied populations. For this reason, the cultivation of seedlings from seeds obtained in more than one population seems the most appropriate strategy for reforestation purposes. Even though the most isolated populations are also the ones with highest genetic structure, all populations of M. umbellata included in this study revealed to be an important germplasm bank conserved in situ.