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Dehydrated natural feed for dogs: influence on digestibility, immunity, and antioxidant response

Comparative Clinical Pathology 2025年第2期34卷 269-280页

作者： Cecere, Bruno G. O. Zatti, Emerson Bissacotti, Bianca F. Copetti, Priscila M. da Silveira, Marcylene V. Schetinger, Maria Rosa C. Klein, Bruna Suarez, Walter H. C. da Silva, Aleksandro S. Graduate Multicenter Program in Biochemistry and Molecular Biology University of the State of Santa Catarina (UDESC) Lages Brazil Graduate Program in Animal Science Universidade Federal de Santa Maria Santa Maria Brazil Graduate Program in Toxicological Biochemistry Universidade Federal de Santa Maria Santa Maria Brazil Department of Animal Science UDESC Chapecó Brazil Department of Animal Nutrition Tectron Tecnologia e Inovação Toledo Brazil

With the intensification of domestication, companion animals have become precious members of family homes;therefore, there is a constant search for improving the quality of life and well-being of these animals, where nutrition is considered a factor of great relevance. Natural diets appear as an alternative to differentiated feeds for pets, and the dehydration of natural feeds favors their use, maintaining their quality and increasing their shelf life. The present study objective was to determine whether dehydrated natural feed can replace extruded dry feed while maintaining good digestibility without impairing its metabolism, inflammatory/immune responses, and antioxidant status. Ten male beagle dogs housed in an experimental kennel and fed individually were used. They were divided into two groups with five animals each, one group received natural dehydrated feed (DNF), and another consumed commercial dry feed (DCF), calculated from the determination of metabolizable energy (ME) requirements based on the animal’s metabolic weight (BW). The experiment lasted 45 days, with 40 days of adaptation and health assessment and days of feces collection from animals in metabolism cages. At the end of this first phase, after a 10-day interval, the experiment was repeated;however, in this phase, the animals from the DCF group were transferred to the DNF group so that all animals received both feeds. During the 40 days, the animals were weighed, and blood was collected. On the other 5 days, total feces were collected, and the feces score was calculated. The animals in the DNF group showed higher digestibility of digestible fiber and mineral matter and lower digestibility of ether extract and dry matter. The dogs from the DNF group had a higher volume of excreted feces, with higher humidity and a score of 3;for the DCF group, the score was 2. DNF dogs had lower blood leukocyte and granulocyte counts;however, there was a tendency toward increased lymphocytes on day 40. Dogs in the

关键词： Alternative feed Animal health Dry feed Immune response Inflammatory

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Unveiling the Conformational Dynamics of the Histone Tails Using Markov State Modeling

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Journal of Chemical Theory and Computation 2025年第9期21卷 4921-4938页

作者： Patel, Rutika Loverde, Sharon M. Ph.D. Program in Biochemistry The Graduate Center of the City University of New York New York 10016 NY United States Department of Chemistry College of Staten Isl The City University of New York 2800 Victory Boulevard Staten Island 10314 NY United States Ph.D. Program in Chemistry The Graduate Center of the City University of New York New York 10016 NY United States Ph.D. Program in Physics The Graduate Center of the City University of New York New York 10016 NY United States

Biomolecules predominantly exert their function by altering conformational dynamics. The nucleosome core particle (NCP) is the fundamental unit of chromatin. DNA with ∼146 base pairs wraps around the histone octamer to form a nucleosome. The histone octamer is composed of two copies of each histone protein (H3, H4, H2A, and H2B) with a globular core and disordered N-terminal tails. Epigenetic modifications of the histone N-terminal tails play a critical role in regulating the chromatin structure and biological processes such as transcription and DNA repair. Here, we report all-atom molecular dynamics (MD) simulations of the nucleosome at microsecond time scales to construct Markov state models (MSMs) to elucidate distinct conformations of the histone tails. We employ time-lagged independent component analysis (tICA) to capture their essential slow dynamics, with k-means clustering used to discretize the conformational space. MSMs unveil distinct states and transition probabilities to characterize the dynamics and kinetics of the tails. Next, we focus on the H2B tail, which is one of the least studied tails. We show that acetylation increases secondary structure formation with increased transition rates. These findings will aid in understanding the functional implications of tail conformations for nucleosome stability and gene regulation. © 2025 The Authors. Published by American Chemical Society.

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Sex-Dependent Changes in the Gene Expression of UPR-Associated Calcium-Binding Proteins in the STZ–Induced Model of Alzheimer’s Disease

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Molecular Neurobiology 2025年 1-14页

作者： Schultz, Bruna Bobermin, Larissa Menezes, Leonardo Gayger-Dias, Vitor Da Silva, Vanessa-Fernanda Taday, Jéssica Alves, Joelma Tramontina, Francine Zanotto, Caroline Dalmaz, Carla Leite, Marina Concli Leal, Rodrigo Bainy Quincozes-Santos, André Gonçalves, Carlos-Alberto Graduate Program in Biochemistry Department of Biochemistry Universidade Federal do Rio Grande do Sul (UFRGS) Ramiro Barcelos Street 2600 Biochemistry Building Laboratory 33 RS Porto Alegre 90035-003 Brazil Universidade Estadual do Rio Grande do Sul RS Porto Alegre Brazil Biochemistry Laboratory Grupo Hospitalar Conceição RS Porto Alegre Brazil Graduate Program Biochemistry Departament of Biochemistry Universidade Federal de Santa Catarina (UFSC) SC Florianópolis Brazil Graduate Program in Neurosciences Institute of Basic Health Sciences UFRGS RS Porto Alegre Brazil

Although the causes of Alzheimer’s disease (AD) are still unknown, the unfolded protein response (UPR) is considered the basis for the pathogenesis of many degenerative diseases, including AD. The incidence of AD is slightly higher in the female population;however, biases continue to raise questions as to whether gender is a risk factor for the disease, as insulin resistance is. In this study, we used a sporadic model of Alzheimer’s disease, induced by intracerebroventricularly-administered streptozotocin (STZ) in Wistar rats, to evaluate potential modulations in proteins involved in the UPR and the dependence of alterations on the sex of the animals. The rats were evaluated at two time points;4 and 16 weeks post-STZ. At 16 weeks, cognitive deficit was observed in all rats treated with STZ, as well as an increase in glial fibrillary acid protein (GFAP), and a reduction in synaptophysin in the hippocampus. However, at 4 weeks, cognitive deficit was found only in males, in association with a reduction in synaptophysin. With regard to neurochemical changes in the AD model of STZ, we found sex-dependent differences in the gene expression of OASIS (an ATF-6-like UPR sensor in astrocytes), calpastatin (inhibitor protein of calpain 1/2), calpain-10, calcineurin, sorcin and CHOP. Taken together, results obtained herein contribute to the understanding of the pathogenesis of AD and indicate that the STZ-triggered UPR observed may be sex-dependent. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.

关键词： Alzheimer’s disease Astrocyte Calcium-binding protein Sex-dependence Sorcin UPR

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Ion Channels and G-Protein-Coupled Receptors Involved in the Development of Chronic Post-ischemic Pain (CPIP): A Model of Complex Regional Pain Syndrome (CRPS-I)

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Molecular Neurobiology 2025年 1-14页

作者： Ruviaro, Náthaly Andrighetto Rodrigues, Patrícia Frare, Julia Maria Trevisan, Gabriela Graduate Program in Biological Sciences: Toxicological Biochemistry Federal University of Santa Maria (UFSM) RS Santa Maria 97105-900 Brazil Graduate Program in Pharmacology Federal University of Santa Maria (UFSM) RS Santa Maria 97105-900 Brazil

Chronic pain is a physical and emotional sensation that exceeds biological necessity. Complex regional pain syndrome (CRPS) is considered a chronic primary pain condition that can arise after limb trauma, such as surgery, ischemia, and fractures. This type of pain is a multifactorial disorder that predominantly affects one body extremity and occurs either without initial nerve injury (CRPS-I) or with partial or complete nerve injury (CRPS-II). Therefore, CRPS-I is still a painful and debilitating condition without a complete understanding of its underlying mechanisms. This gap in knowledge about CRPS-I pathophysiology contributes to patient suffering, as there is still no standard pharmacological treatment. Preclinical research uses diverse models of CRPS-I, such as chronic post-ischemia pain (CPIP), to better understand its pain activation pathways. Various mechanisms continue to emerge in CPIP, including the role of different G-protein-coupled receptors (GPCRs) and ion channels. In this review, we will focus on the mechanisms surrounding these different GPCRs and ion channels in a model of CRPS-I-induced nociception in rodents (the CPIP model). To date, the primary targets studied in CPIP pathophysiology include transient receptor potential (TRP) and N-methyl-D-aspartate (NMDA) ion channels, as well as cannabinoid, bradykinin, adenosine, adrenergic, and endothelin GPCRs. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.

关键词： Adrenergic Cannabinoids Chronic pain Ischemia Nociception TRP channels

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Synthetic Forms Most Beautiful: Engineering Insights into Self-Organization

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Physiology (Bethesda, Md.) 2025年第4期40卷 0-0页

作者： Xu, Zhejing Chang, Chih-Chia Coyle, Scott M. Department of Biochemistry University of Wisconsin-Madison WI United States Integrated Program in Biochemistry Graduate Program University of Wisconsin-Madison WI United States Biophysics Graduate Program University of Wisconsin-Madison WI United States

Reflecting on the diversity of the natural world, Darwin famously observed that "from so simple a beginning endless forms most beautiful and most wonderful have been, and are being evolved." However, the examples that we are able to observe in nature are a consequence of chance, constrained by selection, drift, and epistasis. Here we explore how the efforts of synthetic biology to build new living systems can expand our understanding of the fundamental design principles that allow life to self-organize biological form, from cellular to organismal levels. We suggest that the ability to impose a length or timescale onto a biological activity is an essential strategy for self-organization in evolved systems and a key design target that is now being realized synthetically at all scales. By learning to integrate these strategies together, we are poised to expand on evolution's success and realize a space of synthetic forms not only beautiful but with diverse applications and transformative potential.

关键词： biological form and function evolution self-organization spatiotemporal control synthetic biology

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The filopodial myosin DdMyo7 is a slow, calcium-regulated motor

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Journal of Biological Chemistry 2025年第5期301卷 108371页

作者： Eddington, Casey Titus, Margaret A. Department of Genetics Cell Biology and Development University of Minnesota MinneapolisMN United States Graduate Program in Biochemistry Molecular Biology and Biophysics University of Minnesota MinneapolisMN United States

MyTH4-FERM (MF) myosins are a family of molecular motors with critical roles in the formation and organization of thin membrane protrusions supported by parallel bundles of actin - filopodia, microvilli, and stereocilia. The amoeboid MF myosin DdMyo7 is essential for filopodia formation but its mechanism of action is unknown. The motor properties of a forced-dimer of the DdMyo7 motor were characterized using an in vitro motility assay to address this question. The DdMyo7 motor associates with two different light chains, the Dictyostelium calmodulins CalA and CalB, whose binding is shown to be sensitive to the presence of calcium. Total internal reflection fluorescence motility assays of the dimerized DdMyo7 motor reveal that it is a slow, processive motor that moves along actin at ∼ 40 nm/sec, and the activity of the motor is significantly reduced in the presence of Ca2+. The speed of DdMyo7 is similar to that of other Myo7 family members such as human Myo7A and fly DmMyo7A, but is at least 10-fold slower than the mammalian filopodial MF myosin, Myo10. The results show that evolutionarily distant native filopodial myosins can promote filopodia elongation using motors with distinct properties, revealing diverse mechanisms of myosin-based filopodia formation. © 2025 The Authors

关键词： Mammals

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Deregulation of Neuroinflammatory and Neurotrophic Factors as Biological Events Triggered by D-Galactose Chronic Administration in Wistar Rats

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Neuromolecular medicine 2025年第1期27卷 41页

作者： Eduarda Behenck Medeiros Sabrina da Silva Francielle Mina Adrielly Vargas Lidio Amanda Boaventura Laura Ceolin de Jesus Michelle Lima Garcez Gabriel Casagrande Zabot Gabriela Piovesan Fenilli Matheus Scarpatto Rodrigues Jade de Oliveira Samira S Valvassori Josiane Budni Laboratory of Experimental Neurology Graduate Program in Health Sciences (PPGCS) University of Southern Santa Catarina (UNESC) Criciúma SC Brazil. Department of Clinical Analysis Postgraduate Program in Pharmacy Federal University of Santa Catarina -UFSC Florianópolis SC Brazil. Department of Biochemistry Postgraduate Program in Biological Sciences: Biochemistry Institute of Basic Health Sciences Federal University of Rio Grande Do Sul Porto Alegre Brazil. Translational Psychiatry Laboratory Graduate Program in Health Sciences (PPGCS) University of Southern Santa Catarina (UNESC) Criciúma Brazil. Laboratory of Experimental Neurology Graduate Program in Health Sciences (PPGCS) University of Southern Santa Catarina (UNESC) Criciúma SC Brazil. josiane.budni@***.

The chronic administration of D-galactose (D-gal) is widely used to model brain senescence in rodents. However, the effects of prolonged oral exposure of D-gal on the neuroinflammatory cytokines in rats remain poorly characterized. Therefore, we administered D-gal (100 mg/kg) in male Wistar rats aged 3-4 months, via oral gavage once a day for 1, 2, 4, 6, or 8 weeks. Cytokine and neurotrophin levels were analyzed using the ELISA method. D-gal administrations for 4, 6, and 8 weeks significantly increased interleukin -1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-4 (IL-4) levels in the frontal cortex and hippocampus. In addition, 4, 6, and 8 weeks of D-gal administration significantly increased interleukin-10 (IL-10) levels in the frontal cortex; however, in the hippocampus, only 6 and 8 weeks of D-gal administration significantly increased the IL-10 levels. In terms of neurotrophin levels, our results demonstrated that 1 week of D-gal administration significantly increased Brain-derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) in the hippocampus. In the frontal cortex, D-gal increased BDNF levels when administered for 1 and 2 weeks and increased NGF levels when administered for only 2 weeks. However, we observed a reduction of BDNF, NGF, and Glial cell line-derived Neurotrophic Factor (GDNF) levels after 6 and 8 weeks of D-gal treatment in the frontal cortex. Moreover, GDNF levels also were reduced after 4 weeks of D-gal administration. These findings suggest that oral D-gal exposure disrupts the balance of cytokines and neurotrophins, which may be an essential mechanism in brain aging and neurodegenerative processes.

关键词： Aging D-galactose Inflammatory cytokine Neurotrophins Senescence

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Methacrylic acid/Tween 80 engineered amorphous calcium phosphate as an effective bioactive reinforcing nanofillers in dental adhesive

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Dental Materials Journal 2025年第2期44卷 190-200页

作者： Maimansomsuk, Siripatsorn Teangrom, Paremai Teanchai, Chayada Sinthuvanich, Chomdao Ruengket, Pakorn Attarataya, Jakrada Akkarachaneeyakorn, Khrongkhwan Department of Chemistry Faculty of Science Kasetsart University Bangkok10900 Thailand Center of Excellence for Innovation in Chemistry Faculty of Science Kasetsart University Bangkok10900 Thailand Research Center Faculty of Dentistry Mahidol University Bangkok10400 Thailand Department of Biochemistry Faculty of Science Kasetsart University Bangkok Thailand Faculty of Science Kasetsart University Bangkok Thailand Genetic Engineering and Bioinformatics Program Graduate School Kasetsart University Bangkok Thailand Nakhon Ratchasima30000 Thailand

Bioactive fillers in dental adhesives are designed to release beneficial ions, such as calcium and phosphate, to help in remineralization process, and preventing secondary caries. Their incorporation also aims to improve the longevity of dental restorations. Herein, CaP nanoparticles were synthesized through a water-in-oil emulsion method using Tween80 as a surfactant and methacrylic acid (MAA). MAA officiated as a co-surfactant and reduced the size of CaP nanoparticle, including improved compatibility with the components of dental adhesive. The incorporation of 2% T80/CaP/MAA nanofillers into dental adhesive demonstrated increased efficiency, as evidenced by a higher degree of conversion (%DC) and greater micro-tensile bond strength (μTBS). More importantly, T80/CaP/ MAA nanofillers were able to induce remineralization process in the dental structure, which was confirmed by EDX mapping and IR imaging. Finally, a cytotoxicity assessment of the dental adhesive containing T80/CaP/MAA showed no significant adverse effects on human fibroblast cells. © 2025, Japanese Society for Dental Materials and Devices. All rights reserved.

关键词： Stem cells

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The pentameric chloride channel BEST1 is activated by extracellular GABA

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Proceedings of the National Academy of Sciences of the United States of America 2025年第16期122卷 e2424474122页

作者： Pant, Swati Tam, Stephanie W. Long, Stephen B. Structural Biology Program Memorial Sloan Kettering Cancer Center New York 10065 NY United States Graduate Program in Biochemistry and Structural Biology Cell and Developmental Biology and Molecular Biology Weill Cornell Medicine Graduate School of Medical Sciences New York 10065 NY United States Graduate Program in Physiology Biophysics and Systems Biology Weill Cornell Medicine Graduate School of Medical Sciences New York 10065 NY United States

Bestrophin-1 (BEST1) is a chloride channel expressed in the eye and other tissues of the body. A link between BEST1 and the principal inhibitory neurotransmitter γ-aminobutyric acid (GABA) has been proposed. The most appreciated receptors for extracellular GABA are the GABA_B G-protein-coupled receptors and the pentameric GABA_A chloride channels, both of which have fundamental roles in the central nervous system. Here, we demonstrate that BEST1 is directly activated by GABA. Through functional studies and atomic-resolution structures of human and chicken BEST1, we identify a GABA binding site on the channel’s extracellular side and determine the mechanism by which GABA binding stabilizes opening of the channel’s central gate. This same gate, “the neck,” is activated by intracellular [Ca²⁺], indicating that BEST1 is controlled by ligands from both sides of the membrane. The studies demonstrate that BEST1, which shares no structural homology with GABA_A receptors, is a GABA-activated chloride channel. The physiological implications of this finding remain to be studied. © 2025 the Author(s).

关键词： activation bestrophin chloride channel GABA receptor

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Mechanisms for DNA Interplay in Eukaryotic Transcription Factors

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Annual review of biophysics 2025年第1期54卷 121-139页

作者： Muñoz, Victor Goluguri, Rama Reddy Ghosh, Catherine Tanielian, Benjamin Sadqi, Mourad CREST Center for Cellular and Biomolecular Machines University of California Merced California USA email: vmunoz3@ucmerced.edu Department of Bioengineering University of California Merced CA United States Department of Biochemistry Stanford University Palo Alto CA United States Chemistry and Biochemistry Graduate Program University of California Merced CA United States

Like their prokaryotic counterparts, eukaryotic transcription factors must recognize specific DNA sites, search for them efficiently, and bind to them to help recruit or block the transcription machinery. For eukaryotic factors, however, the genetic signals are extremely complex and scattered over vast, multichromosome genomes, while the DNA interplay occurs in a varying landscape defined by chromatin remodeling events and epigenetic modifications. Eukaryotic factors are rich in intrinsically disordered regions and are also distinct in their recognition of short DNA motifs and utilization of open DNA interaction interfaces as ways to gain access to DNA on nucleosomes. Recent findings are revealing the profound, unforeseen implications of such characteristics for the mechanisms of DNA interplay. In this review we discuss these implications and how they are shaping the eukaryotic transcription control paradigm into one of promiscuous signal recognition, highly dynamic interactions, heterogeneous DNA scanning, and multiprong conformational control.

关键词： conformational control DNA scanning eukaryotic transcription factors nucleosome targeting promiscuous recognition transcription antenna

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