Article
Immunology
Ekaterina Minskaia, Jesmeen Maimaris, Persephone Jenkins, Adriana Albuquerque, Ying Hong, Despina Eleftheriou, Kimberly Gilmour, Richard C. Grace, Fernando O. Moreira, Bodo Grimbacher, Emma C. Morris, Siobhan O. Burns
Summary: The transcription factor STAT6 plays a crucial role in allergic inflammation. A new study identified a mutation in the STAT6 gene that leads to overactivity of the IL-4 signalling pathway and is associated with early-onset atopic dermatitis, food allergy, asthma, anaphylaxis, and lymphoma. The mutation results in higher levels of STAT6 and phosphorylated STAT6, suggesting an increased risk of lymphomagenesis in patients with this mutation.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Clinical Neurology
Hyun Yong Koh, Jaeson Jang, Sang Hyeon Ju, Ryunhee Kim, Gyu-Bon Cho, Dong Seok Kim, Jong-Woo Sohn, Se-Bum Paik, Jeong Ho Lee
Summary: This study reveals that neurons carrying somatic mutations in MTOR lead to focal epileptogenesis through non-cell-autonomous hyperexcitability of nearby nonmutated neurons. The seizure-triggering hyperexcitability originated from nonmutated neurons near mutation-carrying neurons, which were less excitable. The net balance between excitatory and inhibitory synaptic inputs onto mutated neurons remained unchanged, and inhibition of adenosine kinase reduced the hyperexcitability of nonmutated neurons.
ANNALS OF NEUROLOGY
(2021)
Article
Engineering, Electrical & Electronic
Christopher Robbiano, Mahmood R. Azimi-Sadjadi, Edwin K. P. Chong
Summary: This paper addresses an autonomous exploration problem in which a mobile sensor uses an information-theoretic navigation cost function to efficiently detect and classify objects of interest in an unseen search area. The proposed cost function consists of two information gain terms and a novel closed-form representation derived from the definition of mutual information. Experimental results show that using the proposed cost function can improve search efficiency compared to other methods.
IEEE TRANSACTIONS ON SIGNAL PROCESSING
(2021)
Review
Ophthalmology
Ishwarya Narasimhan, Aishwarya Murali, Krishnakumar Subramanian, Sivaprakash Ramalingam, Sowmya Parameswaran
Summary: Autosomal dominant retinitis pigmentosa is a genetic retinal disease characterized by progressive loss of photoreceptors, caused by mutations in genes that can lead to loss of function or toxic gain of function phenotypes. While gene supplementation may be effective for loss of function, toxic gain of function mutations lack a single approach for treatment.
EUROPEAN JOURNAL OF OPHTHALMOLOGY
(2021)
Review
Pharmacology & Pharmacy
Jacob Helm, Ludger Schoels, Stefan Hauser
Summary: Antisense oligonucleotides (ASOs) are single-stranded nucleic acid strings that can selectively modify protein synthesis. Personalized allele-specific ASO therapies for neurodegenerative diseases target mutant mRNA while preserving wild type mRNA expression.
Article
Mathematics, Interdisciplinary Applications
M. A. Navascues
Summary: This study introduces the concept of quasi-fixed points in non-autonomous discrete dynamical systems in metric spaces and proves their role similar to fixed points in autonomous systems. It also presents sufficient conditions for convergence, including reordering of maps and forward/backward directions, and extends the Banach fixed point theorems.
CHAOS SOLITONS & FRACTALS
(2021)
Article
Biochemistry & Molecular Biology
Grigori Y. Rychkov, Zeeshan Shaukat, Chiao Xin Lim, Rashid Hussain, Ben J. Roberts, Claudia M. Bonardi, Guido Rubboli, Brandon F. Meaney, Robyn Whitney, Rikke S. Moller, Michael G. Ricos, Leanne M. Dibbens
Summary: The effects of various KCNT1 mutations on the severity of neurological disorders were investigated, and a positive correlation was found between the severity of the disorder and the KCNT1 channel open probability at resting membrane potential. This suggests that gain of function KCNT1 mutations cause epilepsy by increasing resting potassium conductance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Ningda Xu, Yi Cai, Jiarui Li, Tianchang Tao, Caifei Liu, Yan Shen, Xiaoxin Li, Leiliang Zhang, Mingwei Zhao, Xuan Shi, Jing Li, Lvzhen Huang
Summary: Using whole-exome sequencing, we identified a candidate disease-causing DNA variant, SNX31, in a Chinese family with familial exudative vitreoretinopathy (FEVR). The SNX31 mutation led to retinal vasculature underdevelopment and phenotypes similar to FEVR-like changes in a mouse model. This study expands our understanding of the molecular pathogenesis of FEVR and may contribute to the development of diagnostic and preventive methods for FEVR.
Article
Biochemistry & Molecular Biology
Ziwen Zheng, Guo Li, Chong Cui, Fang Wang, Xiaohan Wang, Zhijiao Xu, Huiping Guo, Yuxin Chen, Honghai Tang, Daqi Wang, Mingqian Huang, Zheng-Yi Chen, Xingxu Huang, Huawei Li, Geng-Lin Li, Xiaoxiang Hu, Yilai Shu
Summary: The CRISPR/CasRx editing system was used to specifically and precisely reduce the expression of target gene in a mouse model of autosomal-dominant hearing loss, leading to improved hearing performance.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Neurosciences
Liqun Wang, Hassan Bukhari, Linghai Kong, Tracy L. Hagemann, Su-Chun Zhang, Albee Messing, Mel B. Feany
Summary: Using different cell and tissue samples from flies, rats, and humans, researchers found that the process of anastasis can lead to cellular senescence and subsequent death of neurons in a disease called Alexander disease.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Green & Sustainable Science & Technology
Uswatun Hasanah, Muhammed Shah Miran, Mohammad Mahbubur Rahman, Md. Mominul Islam
Summary: The study found that using nano-sized manganese dioxide (MnO2) particles can successfully improve the microstructure flaws of leather, enhance its mechanical properties, and bring the quality to a commercially acceptable level.
JOURNAL OF CLEANER PRODUCTION
(2021)
Article
Multidisciplinary Sciences
Alberto Cabada, Nikolay D. Dimitrov, Jagan Mohan Jonnalagadda
Summary: This article investigates a two-point boundary value problem with separated boundary conditions for a finite nabla fractional difference equation. By constructing an associated Green's function and using Leray-Schauder fixed point theorems, existence results for the considered nonlinear problem are deduced under certain conditions. Examples are provided to demonstrate the applicability of the results.
Article
Multidisciplinary Sciences
Daxin Xu, Wei Qian, Zhenkun Yang, Zhenhao Zhang, Ping Sun, Quan Wan, Ying Yin, Yaling Hu, Lingli Gong, Bo Zhang, Xusheng Yang, Zhening Pu, Peihua Lu, Jian Zou
Summary: Through analyzing the TCGA database, we found that TP53 missense mutations are associated with chromosomal instability and tumor mutation burden in non-small cell lung cancer (NSCLC). The expression of wild-type or mutant p53 could not predict the survival of lung cancer patients, but acetylated p53 was found to be associated with improved survival outcomes in primary NSCLC tissues. Acetylation promotes the ubiquitination and degradation of mutant p53 while enhancing the stability of wild-type p53, and acetylation of a missense p53 mutation prevents oncogenic function and enhances tumor suppressor function.
Article
Multidisciplinary Sciences
Soo Jung Lee, Akhil Kondepudi, Kelly Z. Young, Xiaojie Zhang, Naw May Pearl Cartee, Jijun Chen, Krystal Yujin Jang, Gang Xu, Jimo Borjigin, Michael M. Wang
Summary: CADASIL, the most common inherited cause of vascular dementia and stroke, is caused by mutations in NOTCH3. Pathological NOTCH3 accumulates in the vascular media and is closely related to degeneration of cells. Using immunohistochemical screening, CD63 and CTSH proteins were identified to accumulate in the same location as pathological NOTCH3, revealing new proteins involved in CADASIL pathology.
Article
Multidisciplinary Sciences
Wei Fu, Frank W. Nijhoff
Summary: Based on the direct linearization framework, six novel non-autonomous differential-difference equations were established for discrete Kadomtsev-Petviashvili-type equations. These equations include three in the AKP class, two in the BKP class, and one in the CKP class, with one in the BKP class and one in the CKP class being in (2+2)-dimensional form. All six models maintain the same linear integral equation representations as their associated discrete Kadomtsev-Petviashvili-type equations, ensuring the existence of soliton-type solutions and multi-dimensional consistency from the viewpoint of direct linearization.
PROCEEDINGS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES
(2021)
Article
Multidisciplinary Sciences
Stacey L. Peek, Peter J. Bosch, Ethan Bahl, Brianna J. Iverson, Mrutyunjaya Parida, Preeti Bais, J. Robert Manak, Jacob J. Michaelson, Robert W. Burgess, Joshua A. Weiner
Summary: Akirin2 is critical for maintaining healthy neurons during cortical maturation, with p53 pathways identified as mediators of its functions. Reduction of Trp53 can rescue neurodegeneration caused by Akirin2 loss.
Article
Clinical Neurology
Johnathan Cooper-Knock, Thomas H. Julian, Emily Feneberg, J. Robin Highley, Maurice Sidra, Martin R. Turner, Kevin Talbot, Olaf Ansorge, Scott P. Allen, Tobias Moll, Tatyana Shelkovnikova, Lydia Castelli, Guillaume M. Hautbergue, Christopher Hewitt, Janine Kirby, Stephen B. Wharton, Richard J. Mead, Pamela J. Shaw
Summary: We describe a multi-generational pedigree of amyotrophic lateral sclerosis (ALS) with an autosomal dominant, fully penetrant mutation in the TDP-43 gene. The hallmark pathology of ALS is the mislocalization of TDP-43 and the formation of insoluble TDP-43-positive neuronal cytoplasmic inclusions. While the lower motor neurons showed typical TDP-43 pathology, the motor cortex did not show classical TDP-43-positive inclusions. Despite reduced overall TDP-43 protein expression, the mutated allele was transcribed and translated in patient fibroblasts and motor cortex tissue. Furthermore, the motor cortex tissue carrying the mutation showed atypical TDP-43 protein species but not typical C-terminal fragments. Our findings suggest that the p.Y374X mutation is responsible for a monogenic, fully penetrant form of ALS and expands the molecular phenotypes associated with TDP-43 mutations and ALS.
Article
Clinical Neurology
Carolyn A. Young, John Ealing, Christopher J. McDermott, Tim L. Williams, Ammar Al-Chalabi, Tahir Majeed, Kevin Talbot, Timothy Harrower, Christina Faull, Andrea Malaspina, Joe Annadale, Roger J. Mills, Alan Tennant
Summary: The aim of this study was to investigate whether the WHODAS 2.0 can provide interval level measurement of disability in ALS, allowing parametric analyses. The results showed that the WHODAS 2.0 can be used as a brief patient reported outcome measure to assess disability in ALS and can be used for surveillance of at risk populations.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Clinical Neurology
Puja R. Mehta, Alfredo Iacoangeli, Sarah Opie-Martin, Joke J. F. A. van Vugt, Ahmad Al Khleifat, Andrea Bredin, Lynn Ossher, Peter M. Andersen, Orla Hardiman, Arpan R. Mehta, Pietro Fratta, Kevin Talbot, Ammar Al-Chalabi
Summary: ALS is a heterogeneous neurodegenerative syndrome with a family history observed in up to 20% of cases. Although genetic testing is often limited to those with familial history or young age of onset, it is important to identify all treatable individuals, regardless of age or family history. Restricting genetic testing based on age or family history results in a significant number of missed clinically actionable test results in ALS.
Article
Clinical Neurology
C. A. Young, J. Ealing, C. J. McDermott, T. L. Williams, A. Al-Chalabi, T. Majeed, K. Talbot, T. Harrower, C. Faull, A. Malaspina, J. Annadale, R. J. Mills, A. Tennant
Summary: This study reveals that the prevalence of depression in ALS patients is close to a quarter, with most patients belonging to a single trajectory group. Estimates based on screening for current depressive symptoms underestimate the actual prevalence of depression.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Biochemistry & Molecular Biology
Paige B. Martin, Sarah E. Holbrook, Amy N. Hicks, Timothy J. Hines, Laurent P. Bogdanik, Robert W. Burgess, Gregory A. Cox
Summary: This paragraph discusses Charcot-Marie-Tooth disease, an inherited peripheral neuropathy that is clinically and genetically heterogeneous. Mutations in the IGHMBP2 gene have been found to cause this disease. Researchers created mouse models of CMT2S using CRISPR-cas9 mutagenesis, which will be crucial for understanding the pathogenic mechanisms of IGHMBP2.
HUMAN MOLECULAR GENETICS
(2023)
Article
Neurosciences
David M. Steffen, Camille M. Hanes, Kar Men Mah, Paula Valino Ramos, Peter J. Bosch, Dalton C. Hinz, Jason J. Radley, Robert W. Burgess, Andrew M. Garrett, Joshua A. Weiner
Summary: The establishment of a functional cerebral cortex relies on the proper execution of various developmental steps, which includes dendritic and axonal outgrowth, synaptic connection formation and maturation. Dysregulation of these processes can result in improper neuronal connectivity, including neurodevelopmental disorders. The y-Protocadherins (y-Pcdhs) are involved in multiple aspects of neurodevelopment, including neuronal survival, dendrite arborization, and synapse development. The specific role of each individual y-Pcdh family member remains unclear.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Clinical Neurology
Hugo M. De Oliveira, Arunachalam Soma, Mark R. Baker, Martin R. Turner, Kevin Talbot, Timothy L. Williams
Summary: There is considerable variation in the practice of genetic testing for patients with sporadic motor neurone disease/amyotrophic lateral sclerosis (MND/ALS) and asymptomatic at-risk relatives in specialized care centers in the UK. Many healthcare professionals feel uncomfortable discussing genetic testing with MND/ALS patients and believe that routine genetic testing is not necessary for all patients with apparently sporadic disease. There are concerns regarding testing asymptomatic at-risk individuals and the majority view is that clinical genetics services should play a role in supporting genetic testing in MND/ALS, especially in asymptomatic individuals at risk of carrying pathogenic variants.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Neurosciences
Samuele Negro, Fabio Lauria, Marco Stazi, Toma Tebaldi, Giorgia D'Este, Marco Pirazzini, Aram Megighian, Francesca Lessi, Chiara M. Mazzanti, Gabriele Sales, Chiara Romualdi, Silvia Fillo, Florigio Lista, James N. Sleigh, Andrew P. Tosolini, Giampietro Schiavo, Gabriella Viero, Michela Rigoni
Summary: This study identifies the importance of hydrogen peroxide (H2O2) and its downstream effector, Connective Tissue Growth Factor (Ctgf), in promoting neuromuscular junction (NMJ) regeneration. The study also highlights the striking extracellular matrix (ECM) remodeling process during nerve regeneration upon local H2O2 signaling.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
James N. Sleigh, David Villarroel-Campos, Sunaina Surana, Tahmina Wickenden, Yao Tong, Rebecca L. Simkin, Jose Norberto S. Vargas, Elena R. Rhymes, Andrew P. Tosolini, Steven J. West, Qian Zhang, Xiang-Lei Yang, Giampietro Schiavo
Summary: Gain-of-function mutations in the GARS1 gene result in toxic versions of GlyRS, causing the specific motor and sensory pathology of CMT. Abnormal interactions between GlyRS mutants and proteins such as TrkB underlie CMT2D. Intravital imaging of the sciatic nerve revealed early and persistent disruptions in axonal transport in CMT2D mice. Impairments in BDNF/TrkB were found to be correlated with transport disruption and overall CMT2D neuropathology. Supplementation of muscles with BDNF restored physiological axonal transport in neuropathic mice.
Article
Medicine, Research & Experimental
Anna J. Kordala, Jessica Stoodley, Nina Ahlskog, Muhammad Hanifi, Antonio Garcia Guerra, Amarjit Bhomra, Wooi Fang Lim, Lyndsay M. Murray, Kevin Talbot, Suzan M. Hammond, Matthew J. A. Wood, Carlo Rinaldi
Summary: Spinal muscular atrophy (SMA) is an important genetic cause of infant mortality. The discovery of PRMT inhibitor MS023 shows promising potential for treating SMA and improving the disease phenotype, especially when combined with nusinersen. Further clinical investigation of PRMT inhibition as a standalone or add-on therapy for SMA is warranted.
EMBO MOLECULAR MEDICINE
(2023)
Article
Clinical Neurology
A. L. D. Tadenev, C. L. Hatton, B. Pattavina, T. Mullins, R. Schneider, L. P. Bogdanik, Robert W. Burgess
Summary: Two new mouse models of CMT1X have been generated in this study, which can accurately simulate the pathological mechanisms of human CMT1X-related mutations. Analysis of these mice shows the characteristics of peripheral neuropathy, with thinly myelinated and demyelinated axons, as well as degenerating and regenerating axons mainly in distal motor nerves. Assessment results indicate that these mouse models perform comparably to wild type mice in neuromuscular functional tests.
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2023)
Article
Clinical Neurology
Eleni Christoforidou, Fabio A. Simoes, David Gordon, Kevin Talbot, Majid Hafezparast
Summary: This study examined the intracellular motor neuron pathology of mice with a combination of defective dynein and a TDP-43 mutation. The results showed upregulation of p62 and aggregation of TDP-43, partially recapitulating the human disease. These findings provide new insights into the relationship between dynein and TDP-43 and could be useful for further research on the TDP-43 pathology in ALS.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Clinical Neurology
Alexander G. Thompson, Rachael Marsden, Kevin Talbot, Martin R. Turner
Summary: Using routine health screening blood test data, this study found distinct pre-symptomatic biphasic blood cholesterol trajectories in individuals who later developed amyotrophic lateral sclerosis. The findings suggest that metabolic alterations may occur prior to the onset of motor symptoms in this disease. These findings provide further evidence for the importance of monitoring blood cholesterol levels for early detection and potential preventative therapy in amyotrophic lateral sclerosis.
BRAIN COMMUNICATIONS
(2023)
Article
Clinical Neurology
Jennifer C. Davies, Thanuja Dharmadasa, Alexander G. Thompson, Evan C. Edmond, Katie Yoganathan, Jiali Gao, Kevin Talbot, Martin R. Turner
Summary: A reliable biomarker for diagnosing amyotrophic lateral sclerosis (ALS) across different clinical conditions is necessary. Neurofilament light chain levels are correlated with the progression of disability in ALS patients. Previous studies have only compared neurofilament light chain levels in ALS patients with healthy individuals or controls with diagnoses distinct from ALS. In this study, neurofilament light chain levels were measured in ALS patients referred to a specialized clinic, and it was found that neurofilament light chain levels can confirm ALS diagnosis but have limited ability to exclude alternative diagnoses. The current importance of neurofilament light chain is its potential use in stratifying ALS patients by disease activity and as a biomarker in therapeutic trials.
BRAIN COMMUNICATIONS
(2023)