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Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Neural regeneration research 2025年第3期20卷 725-739页

作者： benjamin r.Helmold Angela Ahrens Zachary Fitzgerald P.Hande Ozdinler Department of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg School of Medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

关键词： ALS2 alsin amyotrophic lateral sclerosis hereditary spastic paraplegia neurodegenerative diseases personalized medicine precision medicine protein interactome protein-protein interactions SPAST spastin

The hamster egg penetration test may decrease intracytoplasmic sperm injection utilization while maintaining high conventional fertilization rates

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Asian Journal of Andrology 2021年第1期23卷 11-15页

作者： Yetunde Ibrahim Brett Einerson Douglas T Carrell benjamin r.emery Erica Johnstone Division of reproductive Endocrinology and Infertility Department of Obstetrics and GynecologyUniversity of UtahSchool of MedicineSalt Lake CityUT 84132USA Division of Maternal-Fetal Medicine Department of Obstetrics and GynecologyUniversity of UtahSchool of MedicineSalt Lake CityUT 84132USA Division of Urology Department of SurgeryUniversity of UtahSchool of MedicineSalt Lake CityUT 84132USA Department of Human Genetics University of UtahSchool of MedicineSalt Lake CityUT 84132USA

This was a cohort study of in vitro fertilization(IVF)subjects at the University of Utah,Salt Lake City(UT,USA)utilizing partner *** where both the hamster egg penetration test(HEPT)and semen analysis were performed within 2 years prior to IVF cycles were stratified into four groups based on a normal or an abnormal HEPT and *** mean conventional and intracytoplasmic sperm injection(ICSI)fertilization rates were calculated in each *** performed a univariate analysis on the primary outcome comparing clinically interesting *** performed a cost-effectiveness analysis of a policy of HEPT versus universal ICSI in couples with an abnormal *** patients with a normal HEPT,there was no difference in the mean conventional fertilization rates between those with a normal and an abnormal *** was no difference in the mean conventional fertilization rates between subjects with a normal morphology without a hamster test and those with a normal HEPT without a morphology *** 1000 simulated cycles with an abnormal morphology,a policy of HEPT was cost saving compared to universal ICSI,yet produced similar fertilization *** HEPT is similar to the World Health Organization edition 5(WHO-5)morphology in predicting successful conventional fertilization while allowing decreased utilization of ICSI.A policy of HEPT for males with abnormal morphology saves cost in selecting couples for a fertilization method.

关键词： conventional fertilization hamster egg penetration test intracytoplasmic sperm injection semen analysis sperm penetration assay

The effect of epigenetic sperm abnormalities on early embryogenesis

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Asian Journal of Andrology 2006年第2期8卷 131-142页

作者： benjamin r. emery Douglas T.Carrel Andrology & IVF Laboratories Department of Physiology Department of Obstetrics and Gynecology School of Medicine University of UtahSalt Lake CityUtah 84108USA

Sperm are a highly specialized cell type derived to deliver the paternal haploid genome to the oocyte. The epigenetic, or gene regulatory, properties and mechanisms of the sperm assist in preparation of the paternal genome to contribute to embryogenesis and the genome of the zygote. Many recent studies have addressed the issue of altered epigenetic processes in the sperm. This review evaluates the current understanding of DNA damage, chromosome aneuploidy, reduced telomere length, malformations of the centrosome, genomic imprinting errors, altered mrNA profiles, and abnormal nuclear packaging in the sperm prior to fertilization and the observed effects on embryogenesis. Attention has also been given to understanding the underlying etiology of sperm with altered epigenetic mechanisms in humans. （Asian J Androl 2006 Mar; 8： 131-142）

关键词： embryogenesis DNA damage imprinting aneuploidy telomere centrosome nuclear packaging male infertility

Machine Learning Techniques in Predicting Hot Deformation Behavior of Metallic Materials

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 713-732页

作者： Petr Opela Josef Walek Jaromír Kopecek Department of Metallurgical Technologies Faculty of Materials Science and TechnologyVSB–Technical University of OstravaOstrava70800Czech Republic FZU—Institute of Physics of the Czech Academy of Sciences Prague18200Czech Republic

In engineering practice,it is often necessary to determine functional relationships between dependent and independent *** relationships can be highly nonlinear,and classical regression approaches cannot always provide sufficiently reliable ***,Machine Learning(ML)techniques,which offer advanced regression tools to address complicated engineering issues,have been developed and widely *** study investigates the selected ML techniques to evaluate their suitability for application in the hot deformation behavior of metallic *** ML-based regression methods of Artificial Neural Networks(ANNs),Support Vector Machine(SVM),Decision Tree regression(DTr),and Gaussian Process regression(GPr)are applied to mathematically describe hot flow stress curve datasets acquired experimentally for a medium-carbon *** the GPr method has not been used for such a regression task before,the results showed that its performance is the most favorable and practically unrivaled;neither the ANN method nor the other studied ML techniques provide such precise results of the solved regression analysis.

关键词： Machine learning Gaussian process regression artificial neural networks support vector machine hot deformation behavior

Fundamentals of modern ground control management in Australian underground coal mines

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International Journal of Mining Science and Technology 2020年第5期30卷 573-582页

作者： Jason emery Ismet Canbulat Chengguo Zhang School of Minerals and Energy resources Engineering University of New South WalesSydneyNSW 2052Australia

Underground coal mining is inherently hazardous,with uncontrolled ground failure regarded as one of only several critical risks for multiple fatality ***,implementation and management of overarching systems and procedures for maintaining strata control is an important step to mitigating the impact of ground failure hazards at a mine site operational *** paper summarised the typical pro-active ground control management system(PGCMS)implemented in various Australian underground coal *** produces approximately 100 million tonnes a year of metallurgical and thermal coal from approximately 30 of the world’s safest longwall mines operating in New South Wales and *** increased longwall productivity required to achieve both high levels of safety and profitability,places significant emphasis on the reliability of pro-active ground control management for longwall mining *** depths,adverse geological conditions,elevated variable stress regimes and weaker ground conditions,coupled with an industry wide need for increased development rates continue to make ground control management *** control management is not only about ground support and pillar design though but also a structured process that requires a coordinated effort from all levels of the workforce to both minimise the occurrence of adverse geotechnical events and mitigate the potential risks when they do *** PGCMS presented in this paper is proven to provide both a safer and more productive mine environment through minimisation of unplanned *** critical elements of the method are presented in detail and demonstrate the utility and value of a ground control management system that has potential for implementation in underground coal mining globally.

关键词： Strata control Ground control Management Longwall Safety risk

Emerging potential of progranulin-dependent SorCS2 signaling in healthy and diseased nervous systems

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Neural regeneration research 2025年第9期20卷 2591-2593页

作者： Alena Salasova Anders Nykjær Danish research Institute of Translational Neuroscience DANDrITE-Nordic EMBL Partnership for Molecular Medicine and Centre of Excellence PROMEMODepartment of BiomedicineAarhus UniversityAarhusDenmark

The formation of the mammalian nervous system and its maturation into sensory,motor,cognitive,and behavioral circuits is a complex process that begins during early embryogenesis and lasts until young *** neurodevelopm... 详细信息

关键词： progr jointly CS2

Proton-pump inhibitor use does not affect semen luality in subfertile men

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Asian Journal of Andrology 2018年第3期20卷 290-293页

作者： Sorena Keihani James r Craig Chong Zhang Angela P Presson Jeremy B Myers William O Brant Kenneth I Aston benjamin r.emery Timothy G Jenkins Douglas T Carrell James M Hotaling Division of Urology Department of Surgery University of Utah Salt Lake City Utah 84132 USA Division of Epidemiology Department of Internal Medicine University of Utah Salt Lake City Utah 84132 USA Andrology and IVF Laboratory Department of Surgery (Urology) University of Utah Salt Lake City Utah 84108 USA

Proton-pump inhibitors （PPIs） are among the most widely used drugs worldwide. PPI use has recently been linked to adverse changes in semen quality in healthy men; however, the effects of PPI use on semen parameters remain largely unknown specifically in cases with male factor infertility. We examined whether PPI use was associated with detrimental effects on semen parameters in a large population of subfertile men. We retrospectively reviewed data from 12 257 subfertile men who had visited our fertility clinic from 2003 to 2013. Patients who reported using any PPIs for 〉3 months before semen sample collection were included; 7698 subfertile men taking no medication served as controls. Data were gathered on patient age, medication use, and conventional semen parameters; patients taking any known spermatotoxic medication were excluded. Linear mixed-effect regression models were used to test the effect of PPI use on semen parameters adjusting for age. A total of 248 patients （258 samples） used PPIs for at least 3 months before semen collection. In regression models, PPI use （either as the only medication or when used in combination with other nonspermatotoxic medications） was not associated with statistically significant changes in semen parameters. To our knowledge, this is the largest study to compare PPI use with semen parameters in subfertile men. Using PPIs was not associated with detrimental effects on semen quality in this retrospective study.

关键词： infertility proton-pump inhibitors semen analysis sperm quality spermatozoa

Matrilinear hierarchy in the American black bear (Ursus americanus)

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Integrative Zoology 2022年第1期17卷 139-155页

作者： benjamin KILHAM James r.SPOTILA Kilham Bear Center LymeNew HampshireUSA Department of Biodiversity Earth and Environmental ScienceDrexel UniversityPhiladelphiaPennsylvaniaUSA

The American black bear(Ursus americanus)was long thought to be solitary and its social organization has not been well ***,we present new data on black bear social *** objectives of the study were to make detailed observations of the behavior of wild black bears to determine their social interactions and *** tested whether black bears interacted socially beyond mating and competing for resources,if black bears tracked relationships and interacted regularly even when resources were not limited,and whether the social structure of a population of black bears was based on a matrilinear *** collected data by direct observation of bears from 1993 to *** of 1210 social interactions at a provisioning site indicated that females compete and form matrilinear *** bears established a hierarchy for food,control of space,and control of younger *** interaction scent marking took place,which suggested that dominant females were conditioning subordinates to their scent *** behavior occurred between related and unrelated bears and helped to establish the social structure of the bear *** on our data,human–bear conflicts can be reduced by behavioral modifications by humans when they encounter *** of bear behavior and the matrilinear hierarchy provide a basis for non-lethal management of bears that find themselves in a bear–human conflict situation.

关键词： bear matrilinear hierarchy New Hampshire rank social behavior Ursus

A comprehensive investigation on nonlinear vibration and bending characteristics of bio-inspired helicoidal laminated composite structures

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 81-100页

作者： S.SAUrABH r.KIrAN D.SINGH r.VAISH V.S.CHAUHAN School of Mechanical and Materials Engineering Indian Institute of Technology Mandi

Bio-inspired helicoidal composite laminates, inspired by the intricate helical structures found in nature, present a promising frontier for enhancing the mechanical properties of structural designs. Hence, this study provides a comprehensive investigation into the nonlinear free vibration and nonlinear bending behavior of bio-inspired composite plates. The inverse hyperbolic shear deformation theory(IHSDT) of plates is employed to characterize the displacement field, with the incorporation of Green-Lagrange nonlinearity. The problem is modeled using the C0finite element method(FEM), and an in-house code is developed in the MATLAB environment to solve it numerically. Various helicoidal layup configurations including helicoidal recursive(Hr), helicoidal exponential(HE), helicoidal semi-circular(HS), linear helicoidal(LH), and Fibonacci helicoidal(FH)with different layup sequences and quasi-isotropic configurations are studied. The model is validated, and parametric studies are conducted. These studies investigate the effects of layup configurations, side-to-thickness ratio, modulus ratios, boundary conditions, and loading conditions at different load amplitudes on the nonlinear vibration and nonlinear bending behaviors of bio-inspired composite plates. The results show that the laminate sequence exerts a substantial impact on both nonlinear natural frequencies and nonlinear bending behaviors. Moreover, this influence varies across different side-to-thickness ratios and boundary conditions of the bio-inspired composite plate.

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