Sort by
Environmental Disclosure of Fuel Station Companies in the Municipality of Mossoró/RN Based on the Corporate Sustainability Index – ISE
Thiago José Lima Rosa
,Jorge Luís de Oliveira Pinto Filho
Posted: 10 March 2026
5-ALA/SFC Mitigates Tau Toxicity via Lowering Oxidative Stress in a Drosophila Model of Tau Toxicity
5-ALA/SFC Mitigates Tau Toxicity via Lowering Oxidative Stress in a Drosophila Model of Tau Toxicity
Arisa Tamura
,Marie Noguchi
,Naoko Nozawa
,Emiko Suzuki
,Kanae Ando
Mitochondrial dysfunctions are believed to contribute to the pathogenesis of tauopathies, a group of neurodegenerative diseases with abnormal accumulation of microtubule-associated protein tau. The combination of 5-aminolevulinic acid (5-ALA) and sodium ferrous citrate (SFC) is known to improve mitochondrial functions. Here, we report that 5-ALA combined with SFC (5-ALA/SFC) improves mitochondrial functions and mitigates neurodegeneration in transgenic Drosophila expressing human tau. We found that tau reduces ATP levels, decreases mitochondrial distribution to neurites, and increases mitochondrial reactive oxygen species (ROS). Expression of oxidative phosphorylation (OXPHOS) genes was upregulated and activities of complexes I and IV were elevated. Feeding 5-ALA/SFC to tau flies lowers oxidative damages without correcting OXPHOS activities or mitochondrial distribution. 5-ALA/SFC treatment suppressed pathological tau phosphorylation and mitigated tau-induced neurodegeneration. Our results suggest that 5-ALA/SFC decreases a neurodegenerative pathway involving tau, mitochondria, and ROS.
Mitochondrial dysfunctions are believed to contribute to the pathogenesis of tauopathies, a group of neurodegenerative diseases with abnormal accumulation of microtubule-associated protein tau. The combination of 5-aminolevulinic acid (5-ALA) and sodium ferrous citrate (SFC) is known to improve mitochondrial functions. Here, we report that 5-ALA combined with SFC (5-ALA/SFC) improves mitochondrial functions and mitigates neurodegeneration in transgenic Drosophila expressing human tau. We found that tau reduces ATP levels, decreases mitochondrial distribution to neurites, and increases mitochondrial reactive oxygen species (ROS). Expression of oxidative phosphorylation (OXPHOS) genes was upregulated and activities of complexes I and IV were elevated. Feeding 5-ALA/SFC to tau flies lowers oxidative damages without correcting OXPHOS activities or mitochondrial distribution. 5-ALA/SFC treatment suppressed pathological tau phosphorylation and mitigated tau-induced neurodegeneration. Our results suggest that 5-ALA/SFC decreases a neurodegenerative pathway involving tau, mitochondria, and ROS.
Posted: 10 March 2026
Ahmed Negida
,Moaz Elsayed Aboelmagd
,Belal Mohamed Hamed
,Yousef Hawas
,Aya Dziri
,Yasmin Negida
,Brian D. Berman
,Matthew J. Barrett
Background: Parkinson’s disease (PD) is clinically heterogeneous, yet the genetic architecture underlying this heterogeneity remains incompletely understood. We examined the genetic correlates of four complementary PD subtyping frameworks: clinical motor subtype (tremor-dominant [TD] vs. postural instability/gait difficulty [PIGD]), alpha-synuclein seed amplification assay status (SAA+ vs. SAA−), pathological subtype (brain-first vs. body-first, based on REM sleep behavior disorder), and data-driven subtype (diffuse malignant [DM] vs. mild-motor predominant [MMP] vs. intermediate [IM]). Methods: We analyzed 1,597 PD patients from the Parkinson’s Progression Markers Initiative (PPMI) with genetic testing for seven PD-associated genes (LRRK2, GBA, SNCA, PRKN, PINK1, PARK7, VPS35), including specific variant resolution (LRRK2 G2019S, R1441G/C/H; GBA N409S, severe variants; SNCA A53T), and APOE genotyping (ε2/ε3/ε4 alleles). Genetic variant frequencies were compared across subtypes using chi-square or Fisher’s exact tests with Benjamini–Hochberg false discovery rate (FDR) correction. Effect sizes were quantified using Cramér’s V. Multivariable logistic regression (statsmodels) estimated adjusted odds ratios with Wald-based 95% confidence intervals. Results: Among 1,390 genotyped PD patients, LRRK2 carriers constituted 13.7% (190/1,390; 170 G2019S, 18 R1441G/C/H), GBA 8.6% (119/1,390; 96 N409S, 23 severe), and SNCA 2.0% (28/1,390; all A53T). APOE ε4 carriers comprised 23.4% (323/1,380). SAA-negative patients were markedly enriched for LRRK2 variants (37.1% vs. 10.2%, P = 3.7 × 10⁻¹⁹, q < 0.001, V = 0.25), driven by G2019S (28.5% vs. 9.6%, P = 4.9 × 10⁻¹¹, q < 0.001) and R1441G/C/H (7.9% vs. 0.5%, P = 2.7 × 10⁻¹², q < 0.001). Body-first PD was enriched for GBA carriers (12.3% vs. 6.7%, P = 0.004, q = 0.021) and depleted for LRRK2 (7.9% vs. 15.0%, P = 0.002, q = 0.013). The DM subtype carried the highest GBA frequency (14.0% vs. MMP 5.9%, P < 0.001, q = 0.003). After FDR correction, 10 of 48 univariate tests remained significant. Clinical subtypes (TD vs. PIGD) showed only nominal LRRK2 differences that did not survive FDR correction. APOE genotype did not differ across any framework. Conclusions: PD subtypes defined by alpha-synuclein pathology (SAA), pathological onset pattern (brain-first/body-first), and data-driven classification (DM/MMP/IM) show distinct genetic profiles that survive multiple comparison correction. LRRK2 variants strongly associate with SAA-negativity (V = 0.25); GBA variants associate with the severe body-first onset and the diffuse malignant subtype.
Background: Parkinson’s disease (PD) is clinically heterogeneous, yet the genetic architecture underlying this heterogeneity remains incompletely understood. We examined the genetic correlates of four complementary PD subtyping frameworks: clinical motor subtype (tremor-dominant [TD] vs. postural instability/gait difficulty [PIGD]), alpha-synuclein seed amplification assay status (SAA+ vs. SAA−), pathological subtype (brain-first vs. body-first, based on REM sleep behavior disorder), and data-driven subtype (diffuse malignant [DM] vs. mild-motor predominant [MMP] vs. intermediate [IM]). Methods: We analyzed 1,597 PD patients from the Parkinson’s Progression Markers Initiative (PPMI) with genetic testing for seven PD-associated genes (LRRK2, GBA, SNCA, PRKN, PINK1, PARK7, VPS35), including specific variant resolution (LRRK2 G2019S, R1441G/C/H; GBA N409S, severe variants; SNCA A53T), and APOE genotyping (ε2/ε3/ε4 alleles). Genetic variant frequencies were compared across subtypes using chi-square or Fisher’s exact tests with Benjamini–Hochberg false discovery rate (FDR) correction. Effect sizes were quantified using Cramér’s V. Multivariable logistic regression (statsmodels) estimated adjusted odds ratios with Wald-based 95% confidence intervals. Results: Among 1,390 genotyped PD patients, LRRK2 carriers constituted 13.7% (190/1,390; 170 G2019S, 18 R1441G/C/H), GBA 8.6% (119/1,390; 96 N409S, 23 severe), and SNCA 2.0% (28/1,390; all A53T). APOE ε4 carriers comprised 23.4% (323/1,380). SAA-negative patients were markedly enriched for LRRK2 variants (37.1% vs. 10.2%, P = 3.7 × 10⁻¹⁹, q < 0.001, V = 0.25), driven by G2019S (28.5% vs. 9.6%, P = 4.9 × 10⁻¹¹, q < 0.001) and R1441G/C/H (7.9% vs. 0.5%, P = 2.7 × 10⁻¹², q < 0.001). Body-first PD was enriched for GBA carriers (12.3% vs. 6.7%, P = 0.004, q = 0.021) and depleted for LRRK2 (7.9% vs. 15.0%, P = 0.002, q = 0.013). The DM subtype carried the highest GBA frequency (14.0% vs. MMP 5.9%, P < 0.001, q = 0.003). After FDR correction, 10 of 48 univariate tests remained significant. Clinical subtypes (TD vs. PIGD) showed only nominal LRRK2 differences that did not survive FDR correction. APOE genotype did not differ across any framework. Conclusions: PD subtypes defined by alpha-synuclein pathology (SAA), pathological onset pattern (brain-first/body-first), and data-driven classification (DM/MMP/IM) show distinct genetic profiles that survive multiple comparison correction. LRRK2 variants strongly associate with SAA-negativity (V = 0.25); GBA variants associate with the severe body-first onset and the diffuse malignant subtype.
Posted: 10 March 2026
MetaThink: Empowering Large Reasoning Models with Adaptive Self-Correction at Inference Time
Jiarui Qi
,Haoyu Bian
Posted: 10 March 2026
Entendiendo los Biosimilares: Una Perspectiva Farmacológica para el Médico Clínico - Understanding Biosimilars: A Pharmacological Perspective for Clinical Physicians
Gustavo Lorenzo Moretta
,Rosana Claudia Chaud Covarrubias
Posted: 10 March 2026
Preoperative HALP Score as a Marker of Tumor Aggressiveness and Survival in Surgically Treated Soft Tissue Sarcoma: A Retrospective Cohort Study
Hüseyin Pülat
,Oğuzhan Söyler
,Ünal Öner
,Deniz Öztaşan
,Cüneyt Akyüz
,Cemil Yuksel
Posted: 10 March 2026
Antimicrobial Resistance in Pseudomonas aeruginosa and the Emerging Role of Phage Therapy
Rediet Guta Mideksa
,Alazar Amare Amdiyee
,Alemayehu Godana Birhanu
Posted: 10 March 2026
Is Insulin Resistance a Potential Pathophysiological Mechanism Underlying the Association Between Bladder Cancer and Its Known Risk Factors?
Giovanni Tarantino
,Vincenzo Citro
,Ciro Imbimbo
,Felice Crocetto
Posted: 10 March 2026
A Governance Framework for Urban AI in Climate-Resilient Housing and Infrastructure Prioritization
Reyhaneh Ahmadi
,Kaveh Ghamisi
Posted: 10 March 2026
Multi-Radar Trajectory Planning Method Based on Imitation Learning
Xuchao Gao
,Mingqiang Li
,Kai Guan
,Jianjun Ge
Posted: 10 March 2026
The Black Cotton: Bt-Integrated Genetic Design of Naturally Colored Cotton Fibers—Black, Blue, Pink, Green, and Brown—The Five
Basker Palaniswamy
Posted: 10 March 2026
Governing Open Educational Resources as Sustainable Knowledge Commons: A Policy and Institutional Framework for Higher Education
Adeeb Obaid Alsuhaymi
,Fouad Ahmed Atallah
Posted: 10 March 2026
Solana-Based Agent Networks for Immutable Real-Time Journalism Ensuring Credibility in Evolving Media Landscapes
A Manoj Prabaharan
Posted: 10 March 2026
An Approximate Solution to the Minimum Vertex Cover Problem: The Hallelujah Algorithm
Frank Vega
Posted: 10 March 2026
Social Framework for Hydrogen Policies in Latin America: A Case Study of Argentina
Luciana T. Rattaro
,Yehia F. Khalil
Posted: 10 March 2026
On the Cross-Scale Prospects of the Logarithmically Corrected Gravitational Potential: From Black Hole Singularities to Galactic Rotation
Huang Hai
Posted: 10 March 2026
Multiplicity and Structure of Prime Numbers
Ibar Federico Anderson
Posted: 10 March 2026
Algorithmic Sustainability: Governance Conditions for AI-Driven Environmental Decision-Making
Khuloud Ali
,Ghayth Tintawi
,Mohamad Khaled Bassma
,Aftab Haider
Posted: 10 March 2026
Lagun’s Law as a Structural Constraint on Volitional Drive: Straight Validation Across Independent Secondary Datasets
Nikesh Lagun
Posted: 10 March 2026
LLM Alignment Should Go Beyond Harmlessness–Helpfulness and Incorporate Human Agency
Usman Naseem
,Tanmoy Chakraborty
,Kai-Wei Chang
,Mark Dras
,Preslav Nakov
,Nanyun Peng
,Soujanya Poria
Posted: 10 March 2026
of 5,657